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Relationship between ganglioside expression and anti-cancer effects of a plant-derived antibody in breast cancer cells

  • Ju, Won Seok (Department of Biological science, College of Natural Sciences, Wonkwang University) ;
  • Song, Ilchan (Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University) ;
  • Park, Se-Ra (Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University) ;
  • Seo, Sang Young (Department of Biological science, College of Natural Sciences, Wonkwang University) ;
  • Cho, Jin Hyoung (Department of Biological science, College of Natural Sciences, Wonkwang University) ;
  • Min, Sung-Hun (Center of Reproductive Medicine, Good Moonhwa Hospital) ;
  • Kim, Dae-Heon (Department of Biology, Sunchon National University) ;
  • Kim, Ji-Su (National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Sun-Uk (National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Soon Ju (Department of Biological science, College of Natural Sciences, Wonkwang University) ;
  • Ko, Kisung (Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University) ;
  • Choo, Young-Kug (Department of Biological science, College of Natural Sciences, Wonkwang University)
  • 투고 : 2019.08.29
  • 심사 : 2019.09.04
  • 발행 : 2019.09.30

초록

Production of therapeutic monoclonal antibodies (mAbs) using a plant platform has been considered an alternative to the mammalian cell-based production system. A plant-derived mAb CO17-1AK ($mAb^P$ COK) can specifically bind to various types of cancer cell lines. The target protein of $mAb^P$ COK is the epithelial cell adhesion molecule (EpCAM) highly expressed in human epithelial cancer cells, including breast and colorectal cancer cells. It has been hypothesized that its overexpression supports tumor growth and metastasis. A ganglioside is extended well beyond the surfaces of the various cell membranes and has roles in cell growth, inflammation, differentiation, and carcinogenesis. However, the regulation of EpCAM gene expression in breast cancers and the role of gangliosides in oncogenesis are unclear. Here, the purpose of this study was to determine the effects of $mAb^P$ COK on human breast cancer cell proliferation, apoptosis, and ganglioside expression patterns. Our results show that treatment with $mAb^P$ COK suppressed the growth of breast cancer cells and induced apoptotic cell death. It also upregulated the expression of metastasis-related gangliosides in breast cancer cells. Thus, treatment with $mAb^P$ COK may have chemo-preventive therapeutic effects against human breast cancer.

키워드

과제정보

연구 과제 주관 기관 : National Research Foundation of Korea (NRF), KRIBB, System and Synthetic Agrobiotech Center

참고문헌

  1. Ai-Haji M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983-3988 https://doi.org/10.1073/pnas.0530291100
  2. Alfonso LF, Srivenuhopal KS, Arumugam TV, Abbruscato TJ, Weidanz JA, Bhat GJ (2009) Aspirin inhibits camptothecininduced p21CIP1 levels and potentiates apoptosis in human breast cancer cells. Int J Oncol 34:597-608
  3. Ariga T, McDonald MP, Yu RK (2008) Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease-a review. J Lipid Res 49:1157-1175 https://doi.org/10.1194/jlr.R800007-JLR200
  4. Baeuerle PA, Gires O (2007) EpCAM (CD326) finding its role in cancer. Br J Cacner 96:417-423 https://doi.org/10.1038/sj.bjc.6603494
  5. Balzar M, Winter MJ, de Boer CJ, Litvinov SV (1999) The biology of the 17-1A antigen (Ep-CAM). J Mol Med 77:699-712 https://doi.org/10.1007/s001099900038
  6. Basu S, Ma R, Boyle PJ, Mikulla B, Bradley M, Smith B, Basu M, Banerjee S (2004) Apoptosis of human carcinoma cells in the presence of potential anti-cancer drugs: III. Treatment of Colo-205 and SKBR3 cells with: cis-platin, Tamosifen, Melphalan, Betulinic acid, L-PDMP, L-PPMP, and GD3 ganglioside. Glycoconj J 20:563-577 https://doi.org/10.1023/B:GLYC.0000043293.46845.07
  7. Bobowski M, Cazet A, Steenackers A, Delannoy P (2012) Role of complex ganglioside in cancer progression. J Carbohyd Chem 37:1-20 https://doi.org/10.1080/07328303.2017.1420797
  8. Brodzik R, Glogowska M, Bandurska K, Okulicz M, Deka D, Ko K, van der Linden J, Leusen JH, Pogrebnyak N, Golovkin M, Seteplewski Z, Koprowski H (2006) Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells. Proc Natl Acad Sci U S A 103:8804-8809 https://doi.org/10.1073/pnas.0603043103
  9. Coffey RN, Watson RW, O'Neill AJ, Mc Eleny K, Fitzpatrick JM (2002) Androgen-mediated resistance to apoptosis. Prostate 53:300-309 https://doi.org/10.1002/pros.10159
  10. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 104:10158-10163 https://doi.org/10.1073/pnas.0703478104
  11. Daniell H, Streatfield SJ, Wycoff K (2001) Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci 6:219-226 https://doi.org/10.1016/S1360-1385(01)01922-7
  12. David LN, Michael MC (2005) Lipids. Lehninger Principles of Biochemistry 4th edition. W H Freeman & Co. p.357
  13. de Boer CJ, van Krieken JH, Janssen-van Rhijn CM, Litvinov SV (1999) Expression of Ep-CAM in normal, regenerating, metaplastic, and neoplastic liver. J Pathol 188:201-206 https://doi.org/10.1002/(SICI)1096-9896(199906)188:2<201::AID-PATH339>3.0.CO;2-8
  14. Eccles SA, Aboagye EO, Ali S, Anderson AS, Armes J, Berditchevski F, Brennan K, Brown NJ, Bryant HE, Bundred NJ, Burchell JM, Campbell AM, Carroll JS, Clarke RB, Coles CE, Cook GJ, Cox A, Curtin NJ, Dekker LV, Silva Idos S, Duffy SW, Easton DF, Eccles DM, Edwards J, Evans D, Fenlon DF, Flanagan JM, Foster C, Gallagher WM, Garcia-Closas M, Gee JM, Gescher AJ, Goh V, Groves AM, Harvey AJ, Harvie M, Hennessy BT, Hiscox S, Holen I, Howell SJ, Howell A, Hubbard G, Hullbert-Williams N, Hunter MS, Jasani B, Jones LJ, Key TJ, Kirwan CC, Kong A, Kunkler IH, Langdon SP, Leach MO, Mann DJ, Marshall JF, Martin L, Martin SG, Macdougall JE, Miles DW, Miller WR, Morris JR, Moss SM, Mullan P, Natrajan R, O'Connor JP, O'Conner R, Palmieri C, Pharoah PD, Rakha EA, Reed E, Robinson SP, Sahai E, Saxton JM, Schimid P, Smalley MJ, Speirs V, Stein R, Stingl J, Streuli CH, Tutt AN, Velikova G, Walker RA, Watson CJ, Williams KJ, Young LS, Thompson AM (2013) Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Res https://doi.org/10.1186/s13058-017-0911-9
  15. Fukuda M (1996) Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56:2237-2244
  16. Gomord V, Sourrouille C, Fitchette AC, Bardor M, Pagny S, Lerouge P, Faye L (2004) Production and glycosylation of plant-made pharmaceuticals: the antibodies as a challenge. Plant Biotechnol J 2:83-100 https://doi.org/10.1111/j.1467-7652.2004.00062.x
  17. Hyuga S, Yamagata S, Takatsu Y, Nakanishi H, Furukawa K, Yamagata T (1999) Suppression by ganglioside GD1A of migration capability, adhesion to vitronectin and metastatic potential of highly metastatic FBJ-LL cells. Int J Cancer 83:685-691 https://doi.org/10.1002/(SICI)1097-0215(19991126)83:5<685::AID-IJC20>3.0.CO;2-4
  18. Ji MY, Lee YC, Do S 2nd, Nam SY, Jung KY, Kim HM, Park LK, Choo YK (2000) Developmental patterns of mST3GalIV mRNA expression in the mouse: in situ hybridization using DIG-labeled RNA probes. Arch Pharm Res 23:525-530 https://doi.org/10.1007/BF02976584
  19. Ju EJ, Kwak DH, Lee DM, Kim SM, Kim JS, Kim SM, Choi HG, Jung KY, Lee SU, Do SI, Park YI, Choo YK (2005) Pathophysiological implication of ganglioside GM3 in early mouse embryonic development through apoptosis. Arch Pharm Res 28:1057-1064 https://doi.org/10.1007/BF02977402
  20. Jullien S, Bobowski M, Steenackers A, Le Bourhis X, Delannoy P (2013) How do gangliosides regulate RTKs signaling? Cells 2:751-767 https://doi.org/10.3390/cells2040751
  21. Keller R, Geiges M, Keist R (1990) L-arginine-dependent reactive nitrogen intermediates as mediators of tumor cell killing by activated macrophages. Cancer Res 50:1421-1425
  22. Kim EJ, Park SY, Lee JY, Park JH (2013) Fucoidan present in brown algae induces apoptosis of human colon cancer cells. BMC Gastroenterol
  23. Klimp AH, de Vries EG, Scherphof GL, Daemen T (2002) A potential role of macrophage activation in the treatment of cancer. Crit Rev Oncol Hematol 44:143-161 https://doi.org/10.1016/S1040-8428(01)00203-7
  24. Ko K, Steplewski Z, Glogowska M, Koprowski H (2005) Inhibition of tumor growth by plant-derived mAb. Proc Natl Acad Sci U S A 102:7026-7030 https://doi.org/10.1073/pnas.0502533102
  25. Koprowski H, Yusibov V (2001) The green revolution: plants as heterologous expression vectors. Vaccine 19:2735-2741 https://doi.org/10.1016/S0264-410X(00)00511-9
  26. Kudo D, Rayman P, Horton C, Cathcart MK, Bukowski RM, Thornton M, Tannenbaum C, Finke JH (2003) Ganglioside expressed by the renal cell carcinoma cell line SK-RC-45 are involved in tumor-induced apoptosis of T-cells. Cancer Res 63:1676-1683
  27. Lapenna S, Giordano A (2009) Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8:547-566 https://doi.org/10.1038/nrd2907
  28. Lee SM, Ryu JS, Lee JW, Kwak DH, Ko K, Choo YK (2010) Comparison of ganglioside expression between human adipose- and dental pulp-derived stem cell differentiation into osteoblasts. Arch Pharm Res 33:585-591 https://doi.org/10.1007/s12272-010-0413-0
  29. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030-1037 https://doi.org/10.1158/0008-5472.CAN-06-2030
  30. Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO (1994) Ep-CAM: a human epithelial antigen is a hemophilic cell-cell adhesion molecule. J Cell Biol 125:437-446 https://doi.org/10.1083/jcb.125.2.437
  31. Ma JK, Drake PM, Christou P (2003) The production of recombinant pharmaceutical proteins in plants. Natl Rev Gent 4:794-805 https://doi.org/10.1038/nrg1177
  32. Ma R, Koulov A, Moulton C, Basu M, Banerjee S, Goodson H, Basu S (2004) Apoptosis of human breast carcinoma cells in the presence of disialosyl ganglioside: II. Treatment of SKBR3 cells with GD3 and GD1b gangliosides. Glycoconj J 20:319-330 https://doi.org/10.1023/B:GLYC.0000033628.39302.ae
  33. Moldenhauer G, Salnikov AV, Luttgau S, Herr I, Anderl J, Faulstich H (2012) Therapeutic potential of amanitin-conjugated anti-epithelial cell adhesion molecule monoclonal antibody against pancreatic carcinoma. J Natl Cancer Inst 104:622-634 https://doi.org/10.1093/jnci/djs140
  34. Munz M, Murr A, Kvesic M, Rau D, Mangold S, Pflanz S, Lumsden J, Volkland J, Riethmuller G (2010) Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies. Cancer Cell Int
  35. Neumeister P, Pixley FJ, Xiong Y, Xie H, Ashton A, Cammer M, Chan A, Symons M, Stanley ER, Pestell RG (2003) Cyclin D1 governs adhesion and motility of macrophages. Mol Biol Cell 14:2005-2015 https://doi.org/10.1091/mbc.02-07-0102
  36. Paris R, Morales A, Coll O, Sanchez-Reyes A, Garcia-Ruiz C, Fernandez-Checa JC (2002) Ganglioside GD3 sensitizes human hepatoma cells to cancer theraphy. J Biol Chem 277:49870-49876 https://doi.org/10.1074/jbc.M208303200
  37. Regina Todeschini A, Hakomori SI (2008) Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains. Biochim Biophys Acta 1780:421-433 https://doi.org/10.1016/j.bbagen.2007.10.008
  38. Ryu JS, Lee JT, Lim MU, Hwang MR, Hwang KA, Cho YH, Lee JH, Ko K, Choo YK (2013) Plant-derived mAbs have effective anti-cancer activities by increasing ganglioside expression in colon cancers. Biotechnol Lett 35:2031-2038 https://doi.org/10.1007/s10529-013-1318-z
  39. Satyanarayana A, Kaldis P (2009) Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 28:2925-2939 https://doi.org/10.1038/onc.2009.170
  40. Schnell U, Cirnulli V, Giepmans BN (2013) EpCAM: structure and function in health and diases. Biochim Biophys Acta 1828:1989-2001 https://doi.org/10.1016/j.bbamem.2013.04.018
  41. Schoemaker MH, Ros JE, Homan M, Trautwein C, Liston P, Poelstra K, van Goor H, Jansen PL, Moshage H (2002) Cytokine regulation of pro- and anti-apoptotic genes in rat hepathocytes: NF-kappaB-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis. J Hepatol 36:742-750 https://doi.org/10.1016/S0168-8278(02)00063-6
  42. Seol JG, Park WH, Kim ES, Jung CW, Hyun JM, Lee YY, Kim BK (2001) Potential role of caspase-3 and -9 in arsenic trioxide-mediated apoptosis in PCI-1 head and neck cancer cells. Int J Oncol 18:249-255
  43. Shah R, Sabanatham S, Bembridge J, Mearns AJ, Shorrock K (1996) Tumor embolism to LAD during pneumonectomy. A case report. J Cardiovasc Surg (Torino) 37:319-321
  44. Shahrizaila N, Yuki N (2011) Guillain-Barre syndrome animal model: the first proof of molecular mimicry in human autoimmune disorder. J Biomed Biothenol
  45. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10-29 https://doi.org/10.3322/caac.20138
  46. Song I, Kang Y, Lee YK, Myung SC, Ko K (2018) Endoplasmic reticulum retention motif fused to recombinant anti-cancer monoclonal antibody (mAb) CO17-1A affects mAb expression and plant stress response. PLoS One
  47. Spizzo G, Fong D, Wurm M (2011) EpCAM expression in primary tumor tissue and metastasis: an immunohistochemical analysis. J Clin Pathol 64:415-420 https://doi.org/10.1136/jcp.2011.090274
  48. Staib L, Birebent B, Somasundaram R, Purev E, Braumuller H, Leese C, Kuttner N, Li W, Zhu D, Diao J, Wunner W, Speicher D, Beger HG, Song H, Herlyn D (2001) Immunogenicity of recombinant GA733-2E antigen (CO17-1A, EGP, KS1-4, KSA, Ep-CAM) in gastro-intestinal carcinoma patients. Int J Cancer 92:79-87 https://doi.org/10.1002/1097-0215(200102)9999:9999<::AID-IJC1164>3.0.CO;2-J
  49. Strnad J, Hamilton AE, Beavers LS, Gamboa GC, Apelgren LD, Taber LD, Sportsman JR, Bumol TF, Sharp JD, Gadski RA (1989) Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA. Cancer Res. 49:314-317
  50. Svennerholm L (1980) Ganglioside designation. Adv Exp Med Biol
  51. Trizpis M, McLaughlin PM, de Leji LM, Harmsen MC (2007) Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol 171:386-395 https://doi.org/10.2353/ajpath.2007.070152
  52. Verch T, Yusibov V, Koprowski H (1998) Expression and assembly of a full-length monoclonal antibody in plants using a plant virus vector. J Immunol Methods 220:69-75 https://doi.org/10.1016/S0022-1759(98)00149-5
  53. Vogel CA, Galmiche MC, Westermann P, Sun Lin-Quan, Pelegrin A, Silvio F, Delaloye AB, Slosman DO, Mach Jean-Pierre, Buchegger F (1996) Carcinoembryonic antigen expression, antibody localisation and immunophotodetection of human colon cancer liver metastases in nude mice: A model for radioimmunotherapy. Int J Cancer 67:294-302 https://doi.org/10.1002/(SICI)1097-0215(19960717)67:2<294::AID-IJC23>3.0.CO;2-A
  54. Wenqi D, Li W, Shanshan C, Bei C, Yafei Z, Feihu B, Jie L, Daiming F (2009) EpCAM is overexpressed in gastric cancer and its downregulation suppresses proliferation of gastric cancer. J Cancer Res Clin Oncol 135:1277-1285 https://doi.org/10.1007/s00432-009-0569-5
  55. Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, Dirnhofer S (2004) Frequent EpCAM protein expression in human carcinomas. Hum Pathol 35:122-128 https://doi.org/10.1016/j.humpath.2003.08.026
  56. Xiao D, Herman-Antosiewicz A, Antosiewicz J, Xiao H, Brisson M, Lazo JS, Singh SV (2005) Diallyl trisulfide-induced G(2)-M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cds 25 C. Oncogene 24:6256-6268 https://doi.org/10.1038/sj.onc.1208759
  57. Yamashita T, Wada R, Sasaki T, Deng C, Bierfreund U, Sandhoff K, Proia RL (1999) A vital role for glycosphingolipid synthesis during development and differentiation. Proc Natl Acad Sci U S A 96:9142-9147 https://doi.org/10.1073/pnas.96.16.9142
  58. Zha H, Aime-Sempe C, Sato T, Reed JC (1996) Proapoptotic protein Bax heterodimerizes with Bcl-2 and homodimerizes with Bax via a novel domain (BH3) distinct from BH1 and BH2. J Biol Chem 271:7440-7444 https://doi.org/10.1074/jbc.271.13.7440
  59. Zhang ZY, Lu YX, Zhang ZY, Chang YY, Zheng L, Yuan L, Zhang F, Hu YH, Zhang WJ, Li XN (2016) Loss of TINCR expression promotes proliferation, metastasis through activating EpCAM cleavage in colorectal cancer. Oncotarget 7:22639-22649 https://doi.org/10.18632/oncotarget.8141