DOI QR코드

DOI QR Code

Basement Membrane Proteoglycans: Modulators Par Excellence of Cancer Growth and Angiogenesis

  • Iozzo, Renato V. (Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University) ;
  • Zoeller, Jason J. (Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University) ;
  • Nystrom, Alexander (Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University)
  • Received : 2009.04.22
  • Accepted : 2009.04.25
  • Published : 2009.05.31

Abstract

Proteoglycans located in basement membranes, the nanostructures underling epithelial and endothelial layers, are unique in several respects. They are usually large, elongated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more "active configuration" to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical for the evolution of the tumor microenvironment. This review will focus on the functional roles of the major heparan sulfate proteoglycans from basement membrane zones: perlecan, agrin and collagen XVIII, and on their roles in modulating cancer growth and angiogenesis.

Keywords

Acknowledgement

Supported by : National Institutes of Health, NIH NRSA

References

  1. Abdollahi, A., Hahnfeldt, P., Maercker, C., Gr$\"{o}$ne, H.-J., Debus, J., Ansorge, W., Folkman, J., Hlatky, L., and Huber, P.E. (2004). Endostatin's antioangiogenic signaling network. Mol. Cell 13, 649-663 https://doi.org/10.1016/S1097-2765(04)00102-9
  2. Adatia, R., Albini, A., Carlone, S., Giunciuglio, D., Benelli, R., Santi,L., and Noonan, D.M. (1998). Suppression of invasive behavior of melanoma cells by stable expression of anti-sense perlecan cDNA. Ann. Oncol. 8, 1257-1261
  3. Adkins, J.N., Varnum, S.M., Auberry, K.J., Moore, R.J., Angell, N.H., Smith, R.D., Springer, D.L., and Pounds, J.G. (2002). Toward a human blood serum proteome. Analysis by multidimensional separation coupled with mass spectrometry. Mol. Cell. Proteom.1, 947-955 https://doi.org/10.1074/mcp.M200066-MCP200
  4. Arikawa-Hirasawa, E., Watanabe, E., Takami, H., Hassell, J.R., and Yamada, Y. (1999). Perlecan is essential for cartilage and cephalic development. Nature Genet. 23, 354-358 https://doi.org/10.1038/15537
  5. Aviezer, D., Hecht, D., Safran, M., Eisinger, M., David, G., and Yayon, A. (1994). Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor-receptor binding, mitogenesis,and angiogenesis. Cell 79, 1005-1013 https://doi.org/10.1016/0092-8674(94)90031-0
  6. Aviezer, D., Iozzo, R.V., Noonan, D.M., and Yayon, A. (1997). Suppression of autocrine and paracrine functions of basic fibroblast growth factor by stable expression of perlecan antisense cDNA. Mol. Cell. Biol. 17, 1938-1946 https://doi.org/10.1128/MCB.17.4.1938
  7. Baerwald-De La Torre, K., Winzen, U., Halfter, W., and Bixby, J.L. (2004). Glycosaminoglycan-dependent and -independent inhibition of neurite outgrowth by agrin. J. Neurochem. 90, 50-61 https://doi.org/10.1111/j.1471-4159.2004.02454.x
  8. Batmunkh, E., T$\'{a}$trai, P., Szab$\"{o}$ , E., L$\"{o}$ di, C., Holczbauer, A., P$\'{a}$ska, C., Kupcsulik, P., Kiss, A., Schaff, Z., and Kovalszky, I. (2007). Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma. Hum. Pathol. 38, 1508-1515 https://doi.org/10.1016/j.humpath.2007.02.017
  9. Bezakova, G., and Ruegg, M.A. (2003). New insights into the roles of agrin. Nature Rev. Mol. Cell Biol. 4, 295-308 https://doi.org/10.1038/nrm1074
  10. Bix, G., and Iozzo, R.V. (2005). Matrix revolutions: 'tails' of basement-membrane components with angiostatic functions. Trends Cell Biol. 15, 52-60 https://doi.org/10.1016/j.tcb.2004.11.008
  11. Bix, G., and Iozzo, R.V. (2008). Novel interactions of perlecan: Unraveling perlecan's role in angiogenesis. Microsc. Res. 71, 339-348 https://doi.org/10.1002/jemt.20562
  12. Bix, G., Fu, J., Gonzalez, E., Macro, L., Barker, A., Campbell, S., Zutter, M.M., Santoro, S.A., Kim, J.K., H$\"{o}$$\"{o}$k, M., et al. (2004). Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through the $\alpha$2$\beta$1 integrin. J. Cell Biol. 166, 97-109 https://doi.org/10.1083/jcb.200401150
  13. Bix, G., Castello, R., Burrows, M., Zoeller, J.J., Weech, M., Iozzo, R.A., Cardi, C., Thakur, M.T., Barker, C.A., Camphausen, K.C., et al. (2006). Endorepellin in vivo: targeting the tumor vasculature and retarding cancer growth and metabolism. J. Natl. Cancer Inst. 98, 1634-1646 https://doi.org/10.1093/jnci/djj441
  14. Bix, G., Iozzo, R.A., Woodall, B., Burrows, M., McQuillan, A., Campbell, S., Fields, G.B., and Iozzo, R.V. (2007). Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the $\alpha$2$\beta$1 integrin receptor. Blood 109,3745-3748 https://doi.org/10.1182/blood-2006-08-039925
  15. Burgess, R.W., Dickman, D.K., Nunez, L., Glass, D.J., and Sanes, J.R. (2002). Mapping sites responsible for interactions of agrin with neurons. J. Neurochem. 83, 271-284 https://doi.org/10.1046/j.1471-4159.2002.01102.x
  16. Cailhier, J.-F., Sirois, I., Raymond, M.-A., Lepage, S., Laplante, P., Brassard, N., Prat, A., Iozzo, R.V., Pshezhetsky, A.V., and Hebert, M.-J. (2008). Caspase-3 activation triggers extracellular release of cathepsin L and endorepellin proteolysis. J. Biol. Chem. 283, 27220-27229 https://doi.org/10.1074/jbc.M801164200
  17. Chang, J.W., Kang, U.-B., Kim, D.H., Yi, J.K., Lee, J.W., Noh, D.-Y., Lee, C., and Yu, M.-H. (2008). Identification of circulating endorepellin LG3 fragment: Potential use as a serological biomarker for breast cancer. Proteomics Clin. Appl. 2, 23-32 https://doi.org/10.1002/prca.200780049
  18. Clamp, A.R., and Jayson, G.C. (2005). The clinical potential of antiangiogenic fragments of extracellular matrix proteins. Br. J.Cancer 93, 967-972 https://doi.org/10.1038/sj.bjc.6602820
  19. Cohen, I.R., Murdoch, A.D., Naso, M.F., Marchetti, D., Berd, D., and Iozzo, R.V. (1994). Abnormal expression of perlecan proteoglycan in metastatic melanomas. Cancer Res. 54, 5771-5774
  20. Costell, M., Gustafsson, E., Aszodi, A., Morgelin, M., Bloch, W., Hunziker, E., Addicks, K., Timpl, R., and Fassler, R. (1999). Perlecan maintains the integrity of cartilage and some basement membranes. J. Cell Biol. 147, 1109-1122 https://doi.org/10.1083/jcb.147.5.1109
  21. Costell, M., Carmona, R., Gustafsson, E., Gonzalez-Iriarte, M., Fassler, R., and Munoz-Chapuli, R. (2002). Hyperplastic conotruncal endo-cardial cushions and transposition of great arteries in perlecan-null mice. Circ. Res. 91, 158-164 https://doi.org/10.1161/01.RES.0000026056.81424.DA
  22. Denzer, A.J., Sculthess, T., Fauser, C., Schumacher, B., Kammerer, R.A., Engel, J., and Ruegg, M.A. (1998). Electron microscopic structure of agrin and mapping of its binding site in laminin-1. EMBO J. 17, 335-343 https://doi.org/10.1093/emboj/17.2.335
  23. Dhanabal, M., Ramchandran, R., Waterman, M.J., Lu, H., Knebelmann, B., Segal, M., and Sukhatme, V.P. (1999). Endostatin induces endothelial cell apoptosis. J. Biol. Chem. 274, 11721-11726 https://doi.org/10.1074/jbc.274.17.11721
  24. Donahue, J.E., Berzin, T.M., Rafii, M.S., Glass, D.J., Yancopoulos, G.D., Fallon, J.R., and Stopa, E.G. (1999). Agrin in Alzheimer's disease: Altered solubility and abnormal distribution within microvasculature and brain parenchyma. Proc. Natl. Acad. Sci.USA 96, 6468-6472 https://doi.org/10.1073/pnas.96.11.6468
  25. Dong, S., Cole, G.J., and Halfter, W. (2003). Expression of collagen XVIII and localization of its glycosaminoglycan attachment sites. J. Biol. Chem. 278, 1700-1707 https://doi.org/10.1074/jbc.M209276200
  26. Elamaa, H., Snellman, A., Rehn, M., Autio-Harmainen, H., and Pihlajaniemi, T. (2003). Characterization of the human type XVIII collagen gene and proteolytic processing and tissue location of the variant containing a frizzled motif. Matrix Biol. 22, 427-442 https://doi.org/10.1016/S0945-053X(03)00073-8
  27. Farach-Carson, M.C., and Carson, D.D. (2007). Perlecan - a multifunctional extracellular proteoglycan scaffold. Glycobiology 17, 897-905 https://doi.org/10.1093/glycob/cwm043
  28. Ferreras, M., Felbor, U., Lenhard, T., Olsen, B.R., and Delaisse, J. (2000). Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett. 486, 247-251 https://doi.org/10.1016/S0014-5793(00)02249-3
  29. Fukai, N., Eklund, L., Marneros, A.G., Oh, S.P., Keene, D.R., Tamarkin, L., Niemela, M., Ilves, M., Li, E., Pihlajaniemi, T., et al. (2002). Lack of collagen XVIII/endostatin results in eye abnormalities. EMBO J. 21, 1535-1544 https://doi.org/10.1093/emboj/21.7.1535
  30. Fuki, I., Iozzo, R.V., and Williams, K.J. (2000). Perlecan heparan sulfate proteoglycan. A novel receptor that mediates a distinct pathway for ligand catabolism. J. Biol. Chem. 275, 25742-25750 https://doi.org/10.1074/jbc.M909173199
  31. Gautam, M., Noakes, P.G., Moscoso, L., Rupp, F., Scheller, R.H., Merlie, J.P., and Sanes, J.R. (1996). Defective neuromuscular synaptogenesis in agrin-deficient mice. Cell 85, 525-535 https://doi.org/10.1016/S0092-8674(00)81253-2
  32. Gesemann, M., Brancaccio, A., Schumacher, B., and Ruegg, M.A. (1998). Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue. J. Biol. Chem. 273, 600-605 https://doi.org/10.1074/jbc.273.1.600
  33. Ghiselli, G., Eichstetter, I., and Iozzo, R.V. (2001). A role for the perlecan protein core in the activation of the keratinocyte growth factor receptor. Biochem. J. 359, 153-163 https://doi.org/10.1042/0264-6021:3590153
  34. Gianazza, E., Wait, R., Begum,S., Eberini, I., Campagnoli, M., Labo, S., and Galliano, M. (2007). Mapping the 5-50-kDa fraction of human amniotic fluid proteins by 2-DE and ESI-MS. Proteomics Clin. Appl. 1, 167-175 https://doi.org/10.1002/prca.200600543
  35. Gonzalez, E.M., Reed, C.C., Bix, G., Fu, J., Zhang, Y., Gopalakrishnan, B., Greenspan, D.S., and Iozzo, R.V. (2005). BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan. J. Biol. Chem. 280, 7080-7087 https://doi.org/10.1074/jbc.M409841200
  36. Gonz$\'{a}$lez-Iriarte, M., Carmona, R., Perez-Pomares, J.M., Macías, D., Costell, M., and Munoz-Chapuli, R. (2003). Development of the coronary arteries in a murine model of transposition of great arteries. J. Mol. Cell. Cardio. 35, 795-802 https://doi.org/10.1016/S0022-2828(03)00134-2
  37. Grenache, D.G., Zhang, Z., Wells, L.E., Santoro, S.A., Davidson, J.M., and Zutter, M.M. (2006). Wound healing in the $\alpha$2 $\beta$1 integrin-deficient mouse: altered keratinocyte biology and dysregulated matrix metalloproteinase expression. J. Invest. Dermatol. 127, 455-466 https://doi.org/10.1038/sj.jid.5700611
  38. Groffen, A.J.A., Buskens, C.A.F., van Kuppevelt, T.H., Veerkamp, J.H., Monnens, L.A.H., and van den Heuvel, L.P.W.J. (1998). Primary structure and high expression of human agrin in basement membranes of adult lung and kidney. Eur. J. Biochem. 254, 123-128 https://doi.org/10.1046/j.1432-1327.1998.2540123.x
  39. Gronborg, M., Kristiansen, T.Z., Iwahori, A., Chang, R., Reddy, R., Sato, N., Molina, H., Jensen, O.N., Hruban, R.H., Goggins, M.G., et al. (2006). Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol. Cell. Proteom. 5, 157-171 https://doi.org/10.1074/mcp.M500178-MCP200
  40. Halfter, W., Dong, S., Schurer, B., and Cole, G.J. (1998). Collagen XVIII is a basement membrane heparan sulfate proteoglycan. J. Biol. Chem. 273, 25404-25412 https://doi.org/10.1074/jbc.273.39.25404
  41. Handler, M., Yurchenco, P.D., and Iozzo, R.V. (1997). Developmental expression of perlecan during murine embryogenesis. Dev. Dyn. 210, 130-145 https://doi.org/10.1002/(SICI)1097-0177(199710)210:2<130::AID-AJA6>3.0.CO;2-H
  42. Hassell, J.R., Yamada, Y., and Arikawa-Hirasawa, E. (2003). Role of perlecan in skeletal development and diseases. Glycoconj. J. 19, 263-267 https://doi.org/10.1023/A:1025340215261
  43. Hilgenberg, L.G.W., Su, H., Gu, H., O'Dowd, D.K., and Smith, M.A. (2006). $\alpha$3$Na^{+}$/$K^{+}$-ATPase is a neuronal receptor for agrin. Cell 125, 359-369 https://doi.org/10.1016/j.cell.2006.01.052
  44. Hurskainen, M., Eklund, L., Hagg, P.O., Fruttiger, M., Sormunen, R., IIves, M., and Pihlajaniemi, T. (2005). Abnormal maturation of the retinal vasculature in type XVIII collagen/endostatin deficient mice and changes in retinal glial cells due to lack of collagen types XV and XVIII. FASEB J. 19, 1564-1666 https://doi.org/10.1096/fj.04-3101fje
  45. Iozzo, R.V. (1994). Perlecan: a gem of a proteoglycan. Matrix Biol. 14, 203-208 https://doi.org/10.1016/0945-053X(94)90183-X
  46. Iozzo, R.V. (1998). Matrix proteoglycans: from molecular design to cellular function. Annu. Rev. Biochem. 67, 609-652 https://doi.org/10.1146/annurev.biochem.67.1.609
  47. Iozzo, R.V. (2005). Basement membrane proteoglycans: from cellar to ceiling. Nature Rev. Mol. Cell Biol. 6, 646-656 https://doi.org/10.1038/nrm1702
  48. Iozzo, R.V., and Murdoch, A.D. (1996). Proteoglycans of the extracellular environment: clues from the gene and protein side offer novel perspectives in molecular diversity and function. FASEB J. 10, 598-614 https://doi.org/10.1096/fasebj.10.5.8621059
  49. Iozzo, R.V., and San Antonio, J.D. (2001). Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena. J. Clin. Invest. 108, 349-355 https://doi.org/10.1172/JCI13738
  50. Iozzo, R.V., Cohen, I.R., Grassel, S., and Murdoch, A.D. (1994). The biology of perlecan: the multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices. Biochem. J. 302, 625-639 https://doi.org/10.1042/bj3020625
  51. Iozzo, R.V., Pillarisetti, J., Sharma, B., Murdoch, A.D., Danielson, K.G., Uitto, J., and Mauviel, A. (1997). Structural and functional characterization of the human perlecan gene promoter. Transcriptional activation by transforming growth factor-$\beta$ via a nuclear factor 1-binding element. J. Biol. Chem. 272, 5219-5228 https://doi.org/10.1074/jbc.272.8.5219
  52. Kadenhe-Chiweshe, A., Papa, J., McCrudden, K.W., Frischer, J., Bae, J.-O., Huang, J., Fisher, J., Lefkowitch, J.H., Feirt, N., Rudge, J., et al. (2008). Sustained VEGF blockade results in mi croenvironmental sequestration of VEGF by tumors and persistent VEGF receptor-2 activation. Mol. Cancer Res. 6, 1-9 https://doi.org/10.1158/1541-7786.MCR-07-0101
  53. Karumanchi, S.A., Jha, V., Ramchandran, R., Karihaloo, A., Tsiokas, L., Chan, B., Dhanabai, M., Hanai, J.-C., Venkataraman, G., Shriver, Z., et al. (2001). Cell surface glypicans are low-affinity endostatin receptors. Mol. Cell 7, 811-822 https://doi.org/10.1016/S1097-2765(01)00225-8
  54. Kim, Y.-M., Hwang, S., Kim, Y.-M., Pyun, B.-J., Kim, T.-Y., Lee, S.-T., Gho, Y.S., and Kwon, Y.-G. (2002). Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1. J. Biol. Chem. 277, 27872-27879 https://doi.org/10.1074/jbc.M202771200
  55. Kim, N., Stiegler, A.L., Cameron, T.O., Hallock, P.T., Gomez, A.M.,Huang, J.H., Hubbard, S.R., Dustin, M.L., and Burden, S.J. (2008). Lrp4 is a receptor for agrin and forms a complex with MuSK. Cell 135, 334-342 https://doi.org/10.1016/j.cell.2008.10.002
  56. Klein, G., Conzelmann, S., Beck, S., Timpl, R., and Muller, C.A. (1995). Perlecan in human bone marrow: a growth-factor presenting, but anti-adhesive, extracellular matrix component for hematopoietic cells. Matrix Biol. 14, 457-465 https://doi.org/10.1016/0945-053X(95)90003-9
  57. Krishna, J., Shah, Z.A., Merchant, M., Klein, J.B., and Gozal, D. (2006). Urinary protein expression patterns in children with sleep-disordered breathing: preliminary findings. Sleep Med. 7, 221-227 https://doi.org/10.1016/j.sleep.2005.09.010
  58. Kuo, C.J., LaMontagne, K.R., Garcia-Cardena, G., Ackley, B.D., Kalman, D., Park, S., Christofferson, R., Kamihara, J., Ding,Y.-H., Lo, K.-M., et al. (2001). Oligomerization-dependent regulation of motility and morphogenesis by the collagen XVIII NC1/ endostatin domain. J. Cell Biol. 152, 1233-1246 https://doi.org/10.1083/jcb.152.6.1233
  59. Laplante, P., Raymond, M.A., Gagnon, G., Vigneault, N., Sasseville, A.M., Langelier, Y., Bernard, M., Raymond, Y., and Heb$\'{e}$rt, M.-J. (2005). Novel fibrogenic pathways are activated in response to endothelial apoptosis: implications in the pathophysiology of systemic sclerosis. J. Immunol. 174, 5740-5749 https://doi.org/10.4049/jimmunol.174.9.5740
  60. Laplante, P., Raymond, M.-A., Labelle, A., Abe, J.-I., Iozzo, R.V., and Hebert, M.-J. (2006). Perlecan proteolysis induces $\alpha$2 $\beta$1 integrin and src-family kinases dependent anti-apoptotic pathway in fibroblasts in the absence of focal adhesion kinase activation. J. Biol. Chem. 281, 30383-30392 https://doi.org/10.1074/jbc.M606412200
  61. Li, Q., and Olsen, B.R. (2004). Increased angiogenic response in aortic explants of collagen XVIII/endostatin-null mice. Am. J. Pathol. 165, 415-424 https://doi.org/10.1016/S0002-9440(10)63307-X
  62. Lin, W., Burgess, R.W., Dominguez, B., Pfaff, S.L., Sanes, J.R., and Lee, K.-F. (2001). Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature 410, 1057-1064 https://doi.org/10.1038/35074025
  63. Lin, S., Maj, M., Bezakova, G., Magyar, J.P., Brenner, H.R., and Ruegg, M.A. (2008). Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice. Proc. Natl. Acad. Sci. USA 105, 11406-11411 https://doi.org/10.1073/pnas.0801683105
  64. Marneros, A.G., and Olsen, B.R. (2005). Physiological role of collagen XVIII and endostatin. FASEB J. 19, 716-728 https://doi.org/10.1096/fj.04-2134rev
  65. Marneros, A.G., Keene, D.R., Hansen, U., Fukai, N., Moulton, K., Goletz, P.L., Moiseyev, G., Pawlyk, B.S., Halfter, W., Dong, S., et al. (2004). Collagen XVIII/endostatin is essential for vision and retinal pigment epithelial function. EMBO J. 23, 89-99 https://doi.org/10.1038/sj.emboj.7600014
  66. Marneros, A.G., She, H., Zambarakji, H., Hashizume, H., Connolly, E.J., Kim, I., Gragoudas, E.S., Miller, J.W., and Olsen, B.R. (2007). Endogenous endostatin inhibits choroidal neovascularization. FASEB J. 21, 3809-3818 https://doi.org/10.1096/fj.07-8422com
  67. Mathiak, M., Yenisey, C., Grant, D.S., Sharma, B., and Iozzo, R.V. (1997). A role for perlecan in the suppression of growth and invasion in fibrosarcoma cells. Cancer Res. 57, 2130-2136
  68. Matsumoto-Miyai, K., Sokolowska, E., Zurlinden, A., Gee, C.E., Luscher, D., Hettwer, S., Wolfel, J., Ladner, A.P., Ster, J., Gerber, U., et al. (2009). Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage. Cell 136, 1161-1171 https://doi.org/10.1016/j.cell.2009.02.034
  69. Menzel, O., Bekkeheien, R.C., Reymond, A., Fukai, N., Boye, E., Kosztolanyi, G., Aftimos, S., Deutsch, S., Scott, H.S., Olsen, B.R., et al. (2004). Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin. Hum. Mutat. 23, 77-84 https://doi.org/10.1002/humu.10284
  70. Mongiat, M., Taylor, K., Otto, J., Aho, S., Uitto, J., Whitelock, J., and Iozzo, R.V. (2000). The protein core of the proteoglycan perlecan binds specifically to fibroblast growth factor-7. J. Biol. Chem. 275, 7095-7100 https://doi.org/10.1074/jbc.275.10.7095
  71. Mongiat, M., Otto, J., Oldershaw, R., Ferrer, F., Sato, J.D., and Iozzo, R.V. (2001). Fibroblast growth factor-binding protein is a novel partner for perlecan protein core. J. Biol. Chem. 276, 10263-10271 https://doi.org/10.1074/jbc.M011493200
  72. Mongiat, M., Sweeney, S., San Antonio, J.D., Fu, J., and Iozzo, R.V. (2003). Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan. J. Biol. Chem. 278, 4238-4249 https://doi.org/10.1074/jbc.M210445200
  73. Moulton, K.S., Olsen, B.R., Sonn, S., Fukai, N., Zurakowski, D., and Zeng, X. (2004). Loss of collagen XVIII enhances neovascularization and vascular permeability in atherosclerosis. Circulation 110, 1330-1336 https://doi.org/10.1161/01.CIR.0000140720.79015.3C
  74. Nitkin, R.M., Smith, M.A., Magill, C., Fallon, J.R., Yao, Y.-M.M., Wallace, B.G., and McMahan, U.J. (1987). Identification of agrin, a synaptic organizing protein from Torpedo electric organ. J. Cell Biol. 105, 2471-2478 https://doi.org/10.1083/jcb.105.6.2471
  75. Nugent, M.A., and Iozzo, R.V. (2000). Fibroblast growth factor-2. Int. J. Biochem. Cell Biol. 32, 115-120 https://doi.org/10.1016/S1357-2725(99)00123-5
  76. Nugent, M.A., Nugent, H.M., Iozzo, R.V., Sanchack, K., and Edelman, E.R. (2000). Perlecan is required to inhibit thrombosis after deep vascular injury and contributes to endothelial cell-mediated inhibition of intimal hyperplasia. Proc. Natl. Acad. Sci. USA 97, 6722-6727 https://doi.org/10.1073/pnas.97.12.6722
  77. Nyberg, P., Xie, L., and Kalluri, R. (2005). Endogenous inhibitors of angiogenesis. Cancer Res. 65, 3967-3979 https://doi.org/10.1158/0008-5472.CAN-04-2427
  78. Oda, O., Shinzato, T., Ohbayashi, K., Takai, I., Kunimatsu, M., Maeda, K., and Yamanaka, N. (1996). Purification and characterization of perlecan fragment in urine of end-stage renal failure patients. Clin. Chim. Acta 255, 119-132 https://doi.org/10.1016/0009-8981(96)06395-4
  79. Oh, S.P., Kamagata, Y., Muragaki, Y., Timmons, S., Ooshima, A., and Olsen, B.R. (1994a). Isolation and sequencing of cDNAs for proteins with multiple domains of Gly-Xaa-Yaa repeats identify a distinct family of collagenous proteins. Proc. Natl. Acad. Sci. USA 91, 4229-4233 https://doi.org/10.1073/pnas.91.10.4229
  80. Oh, S.P., Warman, M.L., Seldin, M.F., Cheng, S.-D., Knoll, J.H.M., Timmons, S., and Olsen, B.R. (1994b). Cloning of cDNA and genomic DNA encoding human type XVIII collagen and localization of the $\alpha$1(XVIII) collagen gene to mouse chromosome 10 and human chromosome 21. Genomics 19, 494-499 https://doi.org/10.1006/geno.1994.1098
  81. O'Reilly, M.S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W.S., Flynn, E., Birkhead, J.R., Olsen, B.R., and Folkman, J. (1997). Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88, 277-285 https://doi.org/10.1016/S0092-8674(00)81848-6
  82. O'Riordan, E., Orlova, T.N., Mendelev, N., Patschan, D., Kemp, R., Chander, P.N., Hu, R., Hao, G., Gross, S.S., Iozzo, R.V., et al. (2008). Urinary proteomic analysis of chronic renal allograft nephropathy. Proteomics Clin. Appl. 2, 1025-1035 https://doi.org/10.1002/prca.200780137
  83. Raymond, M.-A., Desormeaux, A., Laplante, P., Vigneault, N., Filep, J.G., Landry, K., Pshezhetsky, A.V., and Hebert, M.-J. (2004). Apoptosis of endothelial cells triggers a caspase-dependent anti-apoptotic paracrine loop active on vascular smooth muscle cells. FASEB J. 18, 705-707 https://doi.org/10.1096/fj.03-0573fje
  84. Rehn, M., Hintikka, E., and Pihlajaniemi, T. (1994). Primary structure of the a1 chain of mouse type XVIII collagen, partial structure of the corresponding gene, and comparison of the $\alpha$1(XVIII) chain with its homologue, the $\alpha$1 (XV) collagen chain. J. Biol. Chem. 269, 13929-13935
  85. Rehn, M., Veikkola, T., Kukk-Valdre, E., Nakamura, H., Ilmonen, M., Lombardo, C.R., Pihlajaniemi, T., Alitalo, K., and Vuori, K. (2001). Interaction of endostatin with integrins implicated in angiogenesis. Proc. Natl. Acad. Sci. USA 98, 1024-1029 https://doi.org/10.1073/pnas.031564998
  86. Reif, R., Sales, S., Hettwer, S., Dreier, B., Gisler, C., Wolfel, J., Luscher, D., Zurlinden, A., Stephan, A., Ahmed, S., et al. (2007). Specific cleavage of agrin by neurotrypsin, a synaptic protease linked to mental retardation. FASEB J. 21, 3468-3478 https://doi.org/10.1096/fj.07-8800com
  87. Reiland, J., Sanderson, R.D., Waguespack, M., Barker, S.A., Long, R., Carson, D.D., and Marchetti, D. (2004). Heparanase degrades syndecan-1 and perlecan heparan sulfate: functional implications for tumor cell invasion. J. Biol. Chem. 279, 8047-8055 https://doi.org/10.1074/jbc.M304872200
  88. Robinson, C.J., Mulloy, B., Gallagher, J.T., and Stringer, S.E. (2006). VEGF165-binding sites within heparan sulfate encompass two highly sulfated domains and can be liberated by K5 lyase. J. Biol. Chem. 281, 1731-1740 https://doi.org/10.1074/jbc.M510760200
  89. Rossi, M., Morita, H., Sormunen, R., Airenne, S., Kreivi, M., Wang, L., Fukai, N., Olsen, B.R., Tryggvason, K., and Soininen, R. (2003). Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. EMBO J. 22, 236-245 https://doi.org/10.1093/emboj/cdg019
  90. Saarela, J., Ylikarppa, R., Rehn, M., Purmonen, S., and Pihlajaniemi, T. (1998). Complete primary structure of two variant forms of human type XVIII collagen and tissue-specific differences in the expression of the corresponding transcripts. Matrix Biol. 16, 319-328 https://doi.org/10.1016/S0945-053X(98)90003-8
  91. Sasaki, T., Fukai, N., Mann, K., Gohring, W., Olsen, B.R., and Timpl, R. (1998). Structure, function and tissue forms of the C-terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin. EMBO J. 17, 4249-4256 https://doi.org/10.1093/emboj/17.15.4249
  92. Sauter, B.V., Martinet, O., Zhang, W.-J., Mandeli, J., and Woo, S.L.C. (2001). Adenovirus-mediated gene transfer of endostatin vivo results in high level of transgene expression and inhibition of tumor growth and metastasis. Proc. Natl. Acad. Sci. USA 97, 4802-4807 https://doi.org/10.1073/pnas.090065597
  93. Savor$\'{e} $, C., Zhang, C., Muir, C., Liu, R., Wyrwa, J., Shu, J., Zhau, H.E., Chung, L.W., Carson, D.D., and Farach-Carson, M.C. (2005). Perlecan knockdown in metastatic prostate cancer cells reduces heparin-binding growth factor responses in vitro and tumor growth in vivo. Clin. Exp. Metastasis 22, 377-390 https://doi.org/10.1007/s10585-005-2339-3
  94. Scotton, P., Bleckmann, D., Stebler, M., Sciandra, F., Brancaccio, A., Meier, T., Stetefeld, J., and Ruegg, M.A. (2006). Activation of muscle-specific receptor tyrosine kinase and binding to dystroglycan are regulated by alternative mRNA splicing of agrin. J. Biol. Chem. 281, 36835-36845 https://doi.org/10.1074/jbc.M607887200
  95. Senger, D.R., Perruzzi, C.A., Streit, M., Koteliansky, V.E., de Fougerolles, A.R., and Detmar, M. (2002). The $\alpha$1$\beta$1 and $\alpha$2$\beta$1 integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. Am. J. Pathol. 160, 195-204 https://doi.org/10.1016/S0002-9440(10)64363-5
  96. Seppinen, L., Sormunen, R., Soini, Y., Elamaa, H., Heljasvaara, R., and Pihlajaniemi, T. (2008). Lack of collagen XVIII accelerates cutaneous wound healing, while overexpression of its endostatin domain leads to delayed healing. Matrix Biol. 102, 535-546 https://doi.org/10.1016/j.matbio.2008.03.003
  97. Sharma, B., Handler, M., Eichstetter, I., Whitelock, J., Nugent, M.A., and Iozzo, R.V. (1998). Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo. J. Clin. Invest. 102, 1599-1608 https://doi.org/10.1172/JCI3793
  98. Shichiri, M., and Hirata, Y. (2001). Antiangiogenesis signals by endostatin. FASEB J. 15, 1044-1053 https://doi.org/10.1096/fj.99-1083com
  99. Sudhakar, A., Sugimoto, H., Yang, C., Lively, J., Zeisberg, M., and Kalluri, R. (2003). Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by $\alpha$v$\beta$3 and $\alpha$5$\beta$1 integrins. Proc. Natl. Acad. Sci. USA 100, 4766-4771 https://doi.org/10.1073/pnas.0730882100
  100. Sund, M., Zeisberg, M., and Kalluri, R. (2005). Endogenous stimulators and inhibitors of angiogenesis in gastrointestinal cancers: basic science to clinical application. Gastroenterology 129, 2076-2091 https://doi.org/10.1053/j.gastro.2005.06.023
  101. Suzuki, O.T., Sertie, A.L., Der, K.V., Kok, F., Carpenter, M., Murray, J., Czeizel, A.E., Kliemann, S.E., Rosemberg, S., Monteiro, M., et al. (2002). Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome. Am. J. Hum. Genet. 71, 1320-1329 https://doi.org/10.1086/344695
  102. Sweeney, S.M., DiLullo, G., Slater, S.J., Martinez, J., Iozzo, R.V., Lauer-Fields, J.L., Fields, G.B., and San Antonio, J.D. (2003). Angiogenesis in collagen I requires $\alpha$2$\beta$1 ligation of a GFP$^{*}$GER sequence and possible p38 MAPK activation and focal adhesion disassembly. J. Biol. Chem. 278, 30516-30524 https://doi.org/10.1074/jbc.M304237200
  103. T$\'{a}$trai, P., Dudas, J., Batmunkh, E., M$\'{a}$th$\'{e}$, M., Zalatnai, A., Schaff, Z., Ramadori, G., and Kovalszky, I. (2006). Agrin, a novel basement membrane component in human rat and liver, accumulates in cirrhosis and hepatocellular carcinoma. Lab. Invest. 86, 1149-1160
  104. Thadikkaran, L., Crettaz, D., Siegenthaler, M.A., Gallot, D., Sapin, V., Iozzo, R.V., Queloz, P.A., Schneider, P., and Tissot, J.D. (2005). The role of proteomics in the assessment of premature rupture of fetal membranes. Clin. Chim. Acta 360, 27-36 https://doi.org/10.1016/j.cccn.2005.04.018
  105. Tran, P.-K., Tran-Lundmark, K., Soininen, R., Tryggvason, K., Thyberg, J., and Hedin, U. (2004). Increased intimal hyperplasia and smooth muscle cell proliferation in transgenic mice with heparan sulfate-deficient perlecan. Circ. Res. 94, 550-558 https://doi.org/10.1161/01.RES.0000117772.86853.34
  106. Tsangaris, G.T., Karamessinis, P., Kolialexi, A., Garbis, S.D., Antsaklis, A., Mavrou, A., and Fountoulakis, M. (2006). Proteomic analysis of amniotic fluid in pregnancies with Down syndrome. Proteomics 6, 4410-4419 https://doi.org/10.1002/pmic.200600085
  107. Utriainen, A., Sormunen, R., Kettunen, M., Carvalhaes, L.S., Sajanti, E., Eklund, L., Kauppinen, R., Kitten, G.T., and Pihlajaniemi, T. (2004). Structurally altered basement membranes and hydrocephalus in a type XVIII collagen deficient mouse line. Human Mol. Gen. 13, 2089-2099 https://doi.org/10.1093/hmg/ddh213
  108. Verbeek, M.M., Otte-H$\"{o}$ller, I., van den Born, J., van den Heuvel, L.P.W.J., David, G., Wesseling, P., and de Waal, R.M. (1999). Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer's disease brain. Am. J. Pathol. 155, 2115-2125 https://doi.org/10.1016/S0002-9440(10)65529-0
  109. Vuadens, F., Benay, C., Crettaz, D., Gallot, D., Sapin, V., Schneider, P., Binevenut, W.-V., L$\'{e}$mery, D., Quadroni, M., Dastugue, B., et al. (2003). Identification of biologic markers of the premature rupture of fetal membranes: proteomic approach. Proteomics 3, 1521-1525 https://doi.org/10.1002/pmic.200300455
  110. Warth, A., Kr$\"{o}$ger, S., and Wolburg, H. (2004). Redistribution of aquaporin-4 in human glioblastoma correlates with loss of agrin immunoreactivity from brain capillary basal laminae. Acta Neuropathol. 107, 311-318 https://doi.org/10.1007/s00401-003-0812-0
  111. West, L., Govindraj, P., Koob, T.J., and Hassell, J.R. (2006). Changes in perlecan during chondrocyte differentiation in the fetal bovine rib growth plate. J. Orthop. Res. 24, 1317-1326 https://doi.org/10.1002/jor.20160
  112. Whitelock, J.M., and Iozzo, R.V. (2005). Heparan sulfate: a complex polymer charged with biological activity. Chem. Rev. 105, 2745-2764 https://doi.org/10.1021/cr010213m
  113. Whitelock, J.M., Murdoch, A.D., Iozzo, R.V., and Underwood, P.A. (1996). The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin and heparanases. J. Biol. Chem. 271, 10079-10086 https://doi.org/10.1074/jbc.271.17.10079
  114. Whitelock, J.M., Graham, L.D., Melrose, J., Murdoch, A.D., Iozzo, R.V., and Underwood, P.A. (1999). Human perlecan immunopurified from different endothelial cell sources has different adhesive properties for vascular cells. Matrix Biol. 18, 163-178 https://doi.org/10.1016/S0945-053X(99)00014-1
  115. Whitelock, J.M., Melrose, J., and Iozzo, R.V. (2008). Diverse cell signaling events modulated by perlecan. Biochemistry 47, 11174-11183 https://doi.org/10.1021/bi8013938
  116. Wickstr$\"{o}$m, S.A., Alitalo, K., and Keski-Oja, J. (2005). Endostatin signaling and regulation of endothelial cell-matrix interactions. Adv. Cancer Res. 94, 197-229 https://doi.org/10.1016/S0065-230X(05)94005-0
  117. Winzen, U., Cole, G.J., and Halfter, W. (2003). Agrin is a chimeric proteoglycan with the attachment sites for heparan sulfate/chondroitin sulfate located in two multiple serine-glycine clusters. J. Biol. Chem. 278, 30106-30114 https://doi.org/10.1074/jbc.M212676200
  118. Witmer, A.N., van den Born, J., Vrensen, G.F.J.M., and Schlingemann, R.O. (2001). Vascular localization of heparan sulfate proteoglycans in retinas of patients with diabetes mellitus and in VEGF-induced retinopathy using domain-specific antibodies.Curr. Eye Res. 22, 190-197 https://doi.org/10.1076/ceyr.22.3.190.5519
  119. Woodall, B.P., Nystr$\"{o}$m, A., Iozzo, R.A., Eble, J.A., Niland, S., Krieg, T., Eckes, B., Pozzi, A., and Iozzo, R.V. (2008). Integrin $\alpha$2$\beta$1 is the required receptor for endorepellin angiostatic activity. J. Biol.Chem. 283, 2335-2343 https://doi.org/10.1074/jbc.M708364200
  120. Ylik$\"{a}$rpp$\"{a}$, R., Eklund, L., Sormunen, R., Kontiola, A.I., Utriainen, A., M$\"{a}$$\"{a}$tt$\"{a}$, M., Fukai, N., and Olsen, B.R. (2003). Lack of type XVIII collagen results in anterior ocular defects. FASEB J. 17, 2257-2259 https://doi.org/10.1096/fj.02-1001fje
  121. Yurchenco, P.D., Amenta, P.S., and Patton, B.L. (2004). Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol. 22, 521-538 https://doi.org/10.1016/j.matbio.2003.10.006
  122. Zatterstrom, U.K., Felbor, U., Fukai, N., and Olsen, B.R. (2000). Collagen XVIII/endostatin structure and functional role in angiogenesis. Cell Struct. Funct. 25, 97-101 https://doi.org/10.1247/csf.25.97
  123. Zhang, J., Wang, Y., Chu, Y., Su, L., Gong, Y., Zhang, R., and Xiong, S. (2006). Agrin is involved in lymphocytes activation that is mediated by $\alpha$-dystroglycan. FASEB J. 20, 50-58 https://doi.org/10.1096/fj.04-3303com
  124. Zhang, Z., Ramirez, N.E., Yankeelov, T.E., Li, Z., Ford, L.E., Qi, Y., Pozzi, A., and Zutter, M.M. (2008). $\alpha$2$\beta$1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell-specific manner. Blood 111, 1980-1988 https://doi.org/10.1182/blood-2007-06-094680
  125. Zhou, Z., Wang, J., Cao, R., Morita, H., Soininen, R., Chan, K.M., Liu, B., Cao, Y., and Tryggvason, K. (2004). Impaired angiogenesis, delayed wound healing and retarded tumor growth in perlecan heparan sulfate-deficient mice. Cancer Res. 64, 4699-4702 https://doi.org/10.1158/0008-5472.CAN-04-0810
  126. Zoeller, J.J., and Iozzo, R.V. (2008). Proteomic profiling of endorepellin angiostatic activity on human endothelial cells. Proteome Sci. 6, 7 https://doi.org/10.1186/1477-5956-6-7
  127. Zoeller, J.J., McQuillan, A., Whitelock, J., Ho, S.-Y., and Iozzo, R.V. (2008). A central function for perlecan in skeletal muscle and cardiovascular development. J. Cell Biol. 181, 381-394 https://doi.org/10.1083/jcb.200708022
  128. Zorick, T.S., Mustacchi, Z., Bando, S.Y., Zatz, M., Moreira-Filho, C.A., Olsen, B., and Passos-Bueno, M.R. (2001). High serum endostatin levels in Down syndrome: Implications for improved treatment and prevention of solid tumors. Eur. J. Hum. Genet. 9, 811-814 https://doi.org/10.1038/sj.ejhg.5200721
  129. Zweers, M.C., Davidson, J.M., Pozzi, A., Hallinger, R., Janz, K., Quondamatteo, F., Leutgeb, B., Krieg, T., and Eckes, B. (2007). Integrin $\alpha$2$\beta$1 is required for regulation of murine wound angiogenesis but is dispensable for reepithelialization. J. Invest. Dermatol. 127, 467-478 https://doi.org/10.1038/sj.jid.5700546

Cited by

  1. Introduction to the Tumour Microenvironment Review Series vol.13, pp.a8, 2009, https://doi.org/10.1111/j.1582-4934.2009.00843.x
  2. Role of tyrosine phosphatase SHP-1 in the mechanism of endorepellin angiostatic activity vol.114, pp.23, 2009, https://doi.org/10.1182/blood-2009-02-207134
  3. Structural and mechanistic classification of uronic acid-containing polysaccharide lyases vol.20, pp.12, 2009, https://doi.org/10.1093/glycob/cwq122
  4. Antiproliferative effect of D-glucuronyl C5-epimerase in human breast cancer cells vol.10, pp.None, 2009, https://doi.org/10.1186/1475-2867-10-27
  5. Quantitative and Qualitative Alterations of Heparan Sulfate in Fibrogenic Liver Diseases and Hepatocellular Cancer vol.58, pp.5, 2010, https://doi.org/10.1369/jhc.2010.955161
  6. ${\delta}$-Catenin Affects the Localization and Stability of p120-Catenin by Competitively Interacting with E-Cadherin vol.29, pp.3, 2009, https://doi.org/10.1007/s10059-010-0030-2
  7. Prognostic relevance of collagen XVIII expression in metastatic gastric carcinoma vol.31, pp.3, 2010, https://doi.org/10.1007/s13277-010-0022-z
  8. Basement membrane components are key players in specialized extracellular matrices vol.67, pp.17, 2010, https://doi.org/10.1007/s00018-010-0367-x
  9. Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting vol.277, pp.19, 2009, https://doi.org/10.1111/j.1742-4658.2010.07800.x
  10. Domain structure elucidation of human decorin glycosaminoglycans vol.431, pp.2, 2009, https://doi.org/10.1042/bj20100788
  11. Binding of Procollagen C-Proteinase Enhancer-1 (PCPE-1) to Heparin/Heparan Sulfate vol.285, pp.44, 2009, https://doi.org/10.1074/jbc.m110.141366
  12. The multiple functions of collagen XVIII in development and disease vol.30, pp.2, 2009, https://doi.org/10.1016/j.matbio.2010.11.001
  13. Proteoglycans in cancer biology, tumour microenvironment and angiogenesis vol.15, pp.5, 2009, https://doi.org/10.1111/j.1582-4934.2010.01236.x
  14. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting vol.278, pp.1, 2009, https://doi.org/10.1111/j.1742-4658.2010.07919.x
  15. Tendon Is Covered by a Basement Membrane Epithelium That Is Required for Cell Retention and the Prevention of Adhesion Formation vol.6, pp.1, 2009, https://doi.org/10.1371/journal.pone.0016337
  16. Lymphatic Endothelial Heparan Sulfate Deficiency Results in Altered Growth Responses to Vascular Endothelial Growth Factor-C (VEGF-C) vol.286, pp.17, 2011, https://doi.org/10.1074/jbc.m110.206664
  17. -Glucuronyl C5-epimerase suppresses small-cell lung cancer cell proliferation in vitro and tumour growth in vivo vol.105, pp.1, 2009, https://doi.org/10.1038/bjc.2011.170
  18. Molecular model of human heparanase with proposed binding mode of a heparan sulfate oligosaccharide and catalytic amino acids vol.97, pp.1, 2012, https://doi.org/10.1002/bip.21696
  19. Pro- and anti-angiogenic agents vol.37, pp.3, 2009, https://doi.org/10.1016/j.jmv.2012.02.002
  20. Proteoglycans in prostate cancer vol.9, pp.4, 2009, https://doi.org/10.1038/nrurol.2012.19
  21. Integrin-Mediated Cell-Matrix Interaction in Physiological and Pathological Blood Vessel Formation vol.2012, pp.None, 2009, https://doi.org/10.1155/2012/125278
  22. Breast and Ovarian Cancers : A Survey and Possible Roles for the Cell Surface Heparan Sulfate Proteoglycans vol.60, pp.1, 2012, https://doi.org/10.1369/0022155411428469
  23. Heparan Sulfate Biosynthesis : Methods for Investigation of the Heparanosome vol.60, pp.12, 2009, https://doi.org/10.1369/0022155412460056
  24. An Introduction to Proteoglycans and Their Localization vol.60, pp.12, 2012, https://doi.org/10.1369/0022155412464638
  25. Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis vol.3, pp.None, 2009, https://doi.org/10.3389/fphys.2012.00377
  26. Molecular Alterations Associated with Osteosarcoma Development vol.2012, pp.None, 2009, https://doi.org/10.1155/2012/523432
  27. Golgi-resident PAP-specific 3′-phosphatase-coupled sulfotransferase assays vol.423, pp.1, 2009, https://doi.org/10.1016/j.ab.2012.01.003
  28. Functional Overlap Between Chondroitin and Heparan Sulfate Proteoglycans During VEGF-Induced Sprouting Angiogenesis vol.32, pp.5, 2009, https://doi.org/10.1161/atvbaha.111.240622
  29. Fibroblast EXT1-Levels Influence Tumor Cell Proliferation and Migration in Composite Spheroids vol.7, pp.7, 2009, https://doi.org/10.1371/journal.pone.0041334
  30. Rat Mammary Extracellular Matrix Composition and Response to Ibuprofen Treatment During Postpartum Involution by Differential GeLC–MS/MS Analysis vol.11, pp.10, 2012, https://doi.org/10.1021/pr3003744
  31. Overview of Extracellular Matrix vol.57, pp.1, 2009, https://doi.org/10.1002/0471143030.cb1001s57
  32. Sequence Analysis and Domain Motifs in the Porcine Skin Decorin Glycosaminoglycan Chain vol.288, pp.13, 2009, https://doi.org/10.1074/jbc.m112.437236
  33. Decorin induces rapid secretion of thrombospondin-1 in basal breast carcinoma cells via inhibition of Ras homolog gene family, member A/Rho-associated coiled-coil containing protein kinase 1 vol.280, pp.10, 2009, https://doi.org/10.1111/febs.12148
  34. Biological functions of iduronic acid in chondroitin/dermatan sulfate vol.280, pp.10, 2009, https://doi.org/10.1111/febs.12214
  35. Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer vol.13, pp.None, 2013, https://doi.org/10.1186/1471-2407-13-24
  36. Post-Synthetic Regulation of HS Structure: The Yin and Yang of the Sulfs in Cancer vol.3, pp.None, 2009, https://doi.org/10.3389/fonc.2013.00331
  37. Heparan sulfate-protein binding specificity vol.78, pp.7, 2009, https://doi.org/10.1134/s0006297913070055
  38. Extracellular matrix of secondary lymphoid organs impacts on B-cell fate and survival vol.110, pp.31, 2013, https://doi.org/10.1073/pnas.1218131110
  39. Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4 vol.368, pp.1629, 2013, https://doi.org/10.1098/rstb.2013.0111
  40. Colorectal Cancer and Basement Membranes: Clinicopathological Correlations vol.2014, pp.None, 2009, https://doi.org/10.1155/2014/580159
  41. Assembly, heterogeneity, and breaching of the basement membranes vol.8, pp.3, 2014, https://doi.org/10.4161/cam.28733
  42. Insidious Changes in Stromal Matrix Fuel Cancer Progression vol.12, pp.3, 2009, https://doi.org/10.1158/1541-7786.mcr-13-0535
  43. Myocardial Extracellular Matrix : An Ever-Changing and Diverse Entity vol.114, pp.5, 2009, https://doi.org/10.1161/circresaha.114.302533
  44. Secreted Frizzled-related protein 2 as a target in antifibrotic therapeutic intervention vol.306, pp.6, 2009, https://doi.org/10.1152/ajpcell.00238.2013
  45. The role of vascular-derived perlecan in modulating cell adhesion, proliferation and growth factor signaling vol.35, pp.None, 2009, https://doi.org/10.1016/j.matbio.2014.01.016
  46. Apoptosis in capillary endothelial cells in ageing skeletal muscle vol.13, pp.2, 2009, https://doi.org/10.1111/acel.12169
  47. Delta-catenin promotes the proliferation and invasion of colorectal cancer cells by binding to E-cadherin in a competitive manner with p120 catenin vol.9, pp.1, 2009, https://doi.org/10.1007/s11523-013-0269-6
  48. Glycosaminoglycans in cancer treatment vol.133, pp.suppl2, 2009, https://doi.org/10.1016/s0049-3848(14)50016-3
  49. Vitamin A Deficiency and Alterations in the Extracellular Matrix vol.6, pp.11, 2009, https://doi.org/10.3390/nu6114984
  50. Extracellular matrix assembly: a multiscale deconstruction vol.15, pp.12, 2014, https://doi.org/10.1038/nrm3902
  51. Agrin and Perlecan Mediate Tumorigenic Processes in Oral Squamous Cell Carcinoma vol.9, pp.12, 2009, https://doi.org/10.1371/journal.pone.0115004
  52. Identification and characterization of the gene expression profiles for protein coding and non-coding RNAs of pancreatic ductal adenocarcinomas vol.6, pp.22, 2009, https://doi.org/10.18632/oncotarget.4233
  53. Diverse Roles of Heparan Sulfate and Heparin in Wound Repair vol.2015, pp.None, 2009, https://doi.org/10.1155/2015/549417
  54. Proteoglycan form and function: A comprehensive nomenclature of proteoglycans vol.42, pp.None, 2015, https://doi.org/10.1016/j.matbio.2015.02.003
  55. Decoding the Matrix: Instructive Roles of Proteoglycan Receptors vol.54, pp.30, 2009, https://doi.org/10.1021/acs.biochem.5b00653
  56. The role of perlecan and endorepellin in the control of tumor angiogenesis and endothelial cell autophagy vol.56, pp.5, 2015, https://doi.org/10.3109/03008207.2015.1045297
  57. Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character vol.15, pp.None, 2015, https://doi.org/10.1186/s12885-015-1724-9
  58. Serglycin in Quiescent and Proliferating Primary Endothelial Cells vol.10, pp.12, 2015, https://doi.org/10.1371/journal.pone.0145584
  59. Proteoglycans in liver cancer vol.22, pp.1, 2016, https://doi.org/10.3748/wjg.v22.i1.379
  60. Capillary Electrophoresis–Mass Spectrometry for the Analysis of Heparin Oligosaccharides and Low Molecular Weight Heparin vol.88, pp.3, 2009, https://doi.org/10.1021/acs.analchem.5b04405
  61. Kinetic and Structural Studies of Interactions between Glycosaminoglycans and Langerin vol.55, pp.32, 2009, https://doi.org/10.1021/acs.biochem.6b00555
  62. Endorepellin-evoked Autophagy Contributes to Angiostasis vol.291, pp.37, 2009, https://doi.org/10.1074/jbc.m116.740266
  63. Proteoglycan neofunctions: regulation of inflammation and autophagy in cancer biology vol.284, pp.1, 2009, https://doi.org/10.1111/febs.13963
  64. Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression vol.9, pp.None, 2009, https://doi.org/10.3389/fendo.2018.00483
  65. Proteoglycans as potential biomarkers in odontogenic tumors vol.22, pp.1, 2009, https://doi.org/10.4103/jomfp.jomfp_151_17
  66. A role for collagen type IV in cardiovascular disease? vol.315, pp.3, 2009, https://doi.org/10.1152/ajpheart.00070.2018
  67. Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and Therapeutics vol.118, pp.18, 2009, https://doi.org/10.1021/acs.chemrev.8b00354
  68. Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character vol.18, pp.None, 2009, https://doi.org/10.1186/s12885-018-4597-x
  69. Beyond proteases: Basement membrane mechanics and cancer invasion vol.218, pp.8, 2009, https://doi.org/10.1083/jcb.201903066
  70. Extracellular matrix contribution to skin wound re-epithelialization vol.75, pp.None, 2019, https://doi.org/10.1016/j.matbio.2018.01.002
  71. Spotlight on the Transglutaminase 2-Heparan Sulfate Interaction vol.7, pp.1, 2009, https://doi.org/10.3390/medsci7010005
  72. MMP13 inhibition rescues cognitive decline in Alzheimer transgenic mice via BACE1 regulation vol.142, pp.1, 2009, https://doi.org/10.1093/brain/awy305
  73. Descemet's Membrane Modulation of Posterior Corneal Fibrosis vol.60, pp.4, 2009, https://doi.org/10.1167/iovs.18-26451
  74. Electrospun Nanometer to Micrometer Scale Biomimetic Synthetic Membrane Scaffolds in Drug Delivery and Tissue Engineering: A Review vol.9, pp.5, 2009, https://doi.org/10.3390/app9050910
  75. Silver-Nanoparticle-Mediated Therapies in the Treatment of Pancreatic Cancer vol.2, pp.4, 2009, https://doi.org/10.1021/acsanm.9b00439
  76. The role of microRNAs regulating the expression of matrix metalloproteinases (MMPs) in breast cancer development, progression, and metastasis vol.234, pp.5, 2019, https://doi.org/10.1002/jcp.27445
  77. Coordinated Modulation of Corneal Scarring by the Epithelial Basement Membrane and Descemet's Basement Membrane vol.35, pp.8, 2009, https://doi.org/10.3928/1081597x-20190625-02
  78. Pathogenic effects of agrin V1727F mutation are isoform specific and decrease its expression and affinity for HSPGs and LRP4 vol.28, pp.16, 2019, https://doi.org/10.1093/hmg/ddz081
  79. Increased levels of serum serglycin and agrin is associated with adverse perinatal outcome in early onset preeclampsia vol.38, pp.5, 2009, https://doi.org/10.1080/15513815.2019.1604922
  80. Comparison of the Interactions of Different Growth Factors and Glycosaminoglycans vol.24, pp.18, 2009, https://doi.org/10.3390/molecules24183360
  81. Smart Nanotechnologies to Target Tumor with Deep Penetration Depth for Efficient Cancer Treatment and Imaging vol.2, pp.10, 2009, https://doi.org/10.1002/adtp.201900093
  82. Analysis of Procollagen C-Proteinase Enhancer-1/Glycosaminoglycan Binding Sites and of the Potential Role of Calcium Ions in the Interaction vol.20, pp.20, 2009, https://doi.org/10.3390/ijms20205021
  83. Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan vol.9, pp.None, 2009, https://doi.org/10.3389/fonc.2019.01482
  84. Corneal epithelial basement membrane: Structure, function and regeneration vol.194, pp.None, 2009, https://doi.org/10.1016/j.exer.2020.108002
  85. Corneal wound healing vol.197, pp.None, 2020, https://doi.org/10.1016/j.exer.2020.108089
  86. Descemet's membrane development, structure, function and regeneration vol.197, pp.None, 2009, https://doi.org/10.1016/j.exer.2020.108090
  87. Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment vol.21, pp.18, 2009, https://doi.org/10.3390/ijms21186588
  88. Lycopene enriched tomato extract suppresses chemically induced skin tumorigenesis in mice vol.90, pp.5, 2020, https://doi.org/10.1024/0300-9831/a000597
  89. Angiostatic cues from the matrix: Endothelial cell autophagy meets hyaluronan biology vol.295, pp.49, 2020, https://doi.org/10.1074/jbc.rev120.014391
  90. Key Matrix Remodeling Enzymes: Functions and Targeting in Cancer vol.13, pp.6, 2009, https://doi.org/10.3390/cancers13061441
  91. TGF beta −1, −2 and −3 in the modulation of fibrosis in the cornea and other organs vol.207, pp.None, 2009, https://doi.org/10.1016/j.exer.2021.108594
  92. The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment vol.13, pp.11, 2009, https://doi.org/10.3390/cancers13112788
  93. Descemet's membrane injury and regeneration, and posterior corneal fibrosis, in rabbits vol.213, pp.None, 2009, https://doi.org/10.1016/j.exer.2021.108803