Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Classifying the Linkage between Adipose Tissue Inflammation and Tumor Growth through Cancer-Associated Adipocytes

  • Song, Yae Chan (Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University) ;
  • Lee, Seung Eon (Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University) ;
  • Jin, Young (Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine) ;
  • Park, Hyun Woo (Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University) ;
  • Chun, Kyung-Hee (Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine) ;
  • Lee, Han-Woong (Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University)
  • Received : 2020.05.11
  • Accepted : 2020.06.26
  • Published : 2020.09.30
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Abstract

Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

Keywords

References

  1. Aksu, K., Cagirgan, S., Ozsan, N., Keser, G., and Sahin, F. (2011). NonHodgkin's lymphoma following treatment with etanercept in ankylosing spondylitis. Rheumatol. Int. 31, 1645-1647. https://doi.org/10.1007/s00296-009-1265-0
  2. Bauer, M., Su, G., Casper, C., He, R., Rehrauer, W., and Friedl, A. (2010). Heterogeneity of gene expression in stromal fibroblasts of human breast carcinomas and normal breast. Oncogene 29, 1732- 1740. https://doi.org/10.1038/onc.2009.463
  3. Berraondo, P., Sanmamed, M.F., Ochoa, M.C., Etxeberria, I., Aznar, M.A., Perez-Gracia, J.L., Rodriguez-Ruiz, M.E., Ponz-Sarvise, M., Castanon, E., and Melero, I. (2019). Cytokines in clinical cancer immunotherapy. Br. J. Cancer 120, 6-15. https://doi.org/10.1038/s41416-018-0328-y
  4. Binnewies, M., Roberts, E.W., Kersten, K., Chan, V., Fearon, D.F., Merad, M., Coussens, L.M., Gabrilovich, D.I., Ostrand-Rosenberg, S., Hedrick, C.C., et al. (2018). Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24, 541-550. https://doi.org/10.1038/s41591-018-0014-x
  5. Bochet, L., Lehuede, C., Dauvillier, S., Wang, Y.Y., Dirat, B., Laurent, V., Dray, C., Guiet, R., Maridonneau-Parini, I., Le Gonidec, S., et al. (2013). Adipocytederived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer Res. 73, 5657-5668. https://doi.org/10.1158/0008-5472.CAN-13-0530
  6. Bombardier, C., Peloso, P.M., and Goldsmith, C.H. (1995). Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rheumatoid arthritis. Salsalate-Diclofenac Study Group. J. Rheumatol. 22, 617-624.
  7. Bos, R., van Diest, P.J., de Jong, J.S., van der Groep, P., van der Valk, P., and van der Wall, E. (2005). Hypoxia-inducible factor-1alpha is associated with angiogenesis, and expression of bFGF, PDGF-BB, and EGFR in invasive breast cancer. Histopathology 46, 31-36. https://doi.org/10.1111/j.1365-2559.2005.02045.x
  8. Broadfield, L.A., Marcinko, K., Tsakiridis, E., Zacharidis, P.G., Villani, L., Lally, J.S.V., Menjolian, G., Maharaj, D., Mathurin, T., Smoke, M., et al. (2019). Salicylate enhances the response of prostate cancer to radiotherapy. Prostate 79, 489-497. https://doi.org/10.1002/pros.23755
  9. Bryant, C.S., Munkarah, A.R., Kumar, S., Batchu, R.B., Shah, J.P., Berman, J., Morris, R.T., Jiang, Z.L., and Saed, G.M. (2010). Reduction of hypoxiainduced angiogenesis in ovarian cancer cells by inhibition of HIF-1 alpha gene expression. Arch. Gynecol. Obstet. 282, 677-683. https://doi.org/10.1007/s00404-010-1381-9
  10. Buechler, C., Krautbauer, S., and Eisinger, K. (2015). Adipose tissue fibrosis. World J. Diabetes 6, 548-553. https://doi.org/10.4239/wjd.v6.i4.548
  11. Burge, D. (2003). Etanercept and squamous cell carcinoma. J. Am. Acad. Dermatol. 49, 358-359; author reply 359. https://doi.org/10.1067/S0190-9622(03)00811-9
  12. Cai, Z., Liang, Y., Xing, C., Wang, H., Hu, P., Li, J., Huang, H., Wang, W., and Jiang, C. (2019). Cancer-associated adipocytes exhibit distinct phenotypes and facilitate tumor progression in pancreatic cancer. Oncol. Rep. 42, 2537-2549.
  13. Canestaro, W.J., Forrester, S.H., Raghu, G., Ho, L., and Devine, B.E. (2016). Drug treatment of idiopathic pulmonary fibrosis: systematic review and network meta-analysis. Chest 149, 756-766. https://doi.org/10.1016/j.chest.2015.11.013
  14. Carbone, C., Piro, G., Gaianigo, N., Ligorio, F., Santoro, R., Merz, V., Simionato, F., Zecchetto, C., Falco, G., Conti, G., et al. (2018). Adipocytes sustain pancreatic cancer progression through a non- canonical WNT paracrine network inducing ROR2 nuclear shuttling. Int. J. Obes. (Lond.) 42, 334-343. https://doi.org/10.1038/ijo.2017.285
  15. Chanmee, T., Ontong, P., Konno, K., and Itano, N. (2014). Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel) 6, 1670-1690. https://doi.org/10.3390/cancers6031670
  16. Chonov, D.C., Ignatova, M.M.K., Ananiev, J.R., and Gulubova, M.V. (2019). IL-6 activities in the tumour microenvironment. Part 1. Open Access Maced. J. Med. Sci. 7, 2391-2398. https://doi.org/10.3889/oamjms.2019.589
  17. Coyle, C., Cafferty, F.H., Vale, C., and Langley, R.E. (2016). Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Ann. Oncol. 27, 2184-2195. https://doi.org/10.1093/annonc/mdw410
  18. Cuzick, J., Otto, F., Baron, J.A., Brown, P.H., Burn, J., Greenwald, P., Jankowski, J., La Vecchia, C., Meyskens, F., Senn, H.J., et al. (2009). Aspirin and nonsteroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol. 10, 501-507. https://doi.org/10.1016/S1470-2045(09)70035-X
  19. Dang, Y.F., Jiang, X.N., Gong, F.L., and Guo, X.L. (2018). New insights into molecular mechanisms of rosiglitazone in monotherapy or combination therapy against cancers. Chem. Biol. Interact. 296, 162-170. https://doi.org/10.1016/j.cbi.2018.09.019
  20. Dirat, B., Bochet, L., Dabek, M., Daviaud, D., Dauvillier, S., Majed, B., Wang, Y.Y., Meulle, A., Salles, B., Le Gonidec, S., et al. (2011). Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 71, 2455-2465. https://doi.org/10.1158/0008-5472.CAN-10-3323
  21. Distler, O., Gahlemann, M., and Maher, T.M. (2019). Nintedanib for systemic sclerosis-associated interstitial lung disease. Reply. N. Engl. J. Med. 381, 1596-1597.
  22. Eble, J.A. and Niland, S. (2019). The extracellular matrix in tumor progression and metastasis. Clin. Exp. Metastasis 36, 171-198. https://doi.org/10.1007/s10585-019-09966-1
  23. Erreni, M., Mantovani, A., and Allavena, P. (2011). Tumor-associated macrophages (TAM) and inflammation in colorectal cancer. Cancer Microenviron. 4, 141-154. https://doi.org/10.1007/s12307-010-0052-5
  24. Fang, M., Yuan, J., Peng, C., and Li, Y. (2014). Collagen as a double-edged sword in tumor progression. Tumour Biol. 35, 2871-2882. https://doi.org/10.1007/s13277-013-1511-7
  25. Fischer-Posovszky, P., Wang, Q.A., Asterholm, I.W., Rutkowski, J.M., and Scherer, P.E. (2011). Targeted deletion of adipocytes by apoptosis leads to adipose tissue recruitment of alternatively activated M2 macrophages. Endocrinology 152, 3074-3081. https://doi.org/10.1210/en.2011-1031
  26. Fisher, D.T., Appenheimer, M.M., and Evans, S.S. (2014). The two faces of IL-6 in the tumor microenvironment. Semin. Immunol. 26, 38-47. https://doi.org/10.1016/j.smim.2014.01.008
  27. Greenberg, A.S. and Obin, M.S. (2006). Obesity and the role of adipose tissue in inflammation and metabolism. Am. J. Clin. Nutr. 83, 461S-465S. https://doi.org/10.1093/ajcn/83.2.461S
  28. Hanahan, D. and Coussens, L.M. (2012). Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21, 309-322. https://doi.org/10.1016/j.ccr.2012.02.022
  29. Hanna, E., Quick, J., and Libutti, S.K. (2009). The tumour microenvironment: a novel target for cancer therapy. Oral Dis. 15, 8-17. https://doi.org/10.1111/j.1601-0825.2008.01471.x
  30. Hantel, A. and Larson, R.A. (2018). Imatinib is still recommended for frontline therapy for CML. Blood Adv. 2, 3648-3652. https://doi.org/10.1182/bloodadvances.2018018614
  31. Hasselbalch, H.C., Bjerrum, O.W., Jensen, B.A., Clausen, N.T., Hansen, P.B., Birgens, H., Therkildsen, M.H., and Ralfkiaer, E. (2003). Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis. Am. J. Hematol. 74, 238-242. https://doi.org/10.1002/ajh.10431
  32. Hawley, S.A., Fullerton, M.D., Ross, F.A., Schertzer, J.D., Chevtzoff, C., Walker, K.J., Peggie, M.W., Zibrova, D., Green, K.A., Mustard, K.J., et al. (2012). The ancient drug salicylate directly activates AMP-activated protein kinase. Science 336, 918-922. https://doi.org/10.1126/science.1215327
  33. He, Q., Gao, Z., Yin, J., Zhang, J., Yun, Z., and Ye, J. (2011). Regulation of $HI-1{\alpha}$ activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia. Am. J. Physiol. Endocrinol. Metab. 300, E877-E885. https://doi.org/10.1152/ajpendo.00626.2010
  34. Hinrichs, C.S. and Rosenberg, S.A. (2014). Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol. Rev. 257, 56-71. https://doi.org/10.1111/imr.12132
  35. Hotamisligil, G.S., Shargill, N.S., and Spiegelman, B.M. (1993). Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259, 87-91. https://doi.org/10.1126/science.7678183
  36. Huang, W.K., Tu, H.T., and See, L.C. (2015). Aspirin use on incidence and mortality of gastrointestinal cancers: current state of epidemiological evidence. Curr. Pharm. Des. 21, 5108-5115. https://doi.org/10.2174/1381612821666150915110450
  37. Huh, J.Y., Park, Y.J., Ham, M., and Kim, J.B. (2014). Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol. Cells 37, 365-371. https://doi.org/10.14348/molcells.2014.0074
  38. Hui, L. and Chen, Y. (2015). Tumor microenvironment: sanctuary of the devil. Cancer Lett. 368, 7-13. https://doi.org/10.1016/j.canlet.2015.07.039
  39. Ikeoka, D., Mader, J.K., and Pieber, T.R. (2010). Adipose tissue, inflammation and cardiovascular disease. Rev. Assoc. Med. Bras. 56, 116-121. https://doi.org/10.1590/S0104-42302010000100026
  40. Incio, J., Ligibel, J.A., McManus, D.T., Suboj, P., Jung, K., Kawaguchi, K., Pinter, M., Babykutty, S., Chin, S.M., Vardam, T.D., et al. (2018). Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2. Sci. Transl. Med. 10, eaag0945. https://doi.org/10.1126/scitranslmed.aag0945
  41. Ji, R.C. (2014). Hypoxia and lymphangiogenesis in tumor microenvironment and metastasis. Cancer Lett. 346, 6-16. https://doi.org/10.1016/j.canlet.2013.12.001
  42. Joensuu, H., Wardelmann, E., Sihto, H., Eriksson, M., Sundby Hall, K., Reichardt, A., Hartmann, J.T., Pink, D., Cameron, S., Hohenberger, P., et al. (2017). Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib: an exploratory analysis of a randomized clinical trial. JAMA Oncol. 3, 602-609. https://doi.org/10.1001/jamaoncol.2016.5751
  43. Johnson, A.R., Milner, J.J., and Makowski, L. (2012). The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol. Rev. 249, 218-238. https://doi.org/10.1111/j.1600-065X.2012.01151.x
  44. Jung, H.Y., Fattet, L., and Yang, J. (2015). Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal transition in metastasis. Clin. Cancer Res. 21, 962-968. https://doi.org/10.1158/1078-0432.CCR-13-3173
  45. Kalluri, R. and Zeisberg, M. (2006). Fibroblasts in cancer. Nat. Rev. Cancer 6, 392-401. https://doi.org/10.1038/nrc1877
  46. Kang, J.H., Jang, Y.S., Lee, H.J., Lee, C.Y., Shin, D.Y., and Oh, S.H. (2019). Inhibition of STAT3 signaling induces apoptosis and suppresses growth of lung cancer: good and bad. Lab. Anim. Res. 35, 30. https://doi.org/10.1186/s42826-019-0030-0
  47. Karagiannis, G.S., Poutahidis, T., Erdman, S.E., Kirsch, R., Riddell, R.H., and Diamandis, E.P. (2012). Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue. Mol. Cancer Res. 10, 1403-1418. https://doi.org/10.1158/1541-7786.MCR-12-0307
  48. Khan, T., Muise, E.S., Iyengar, P., Wang, Z.V., Chandalia, M., Abate, N., Zhang, B.B., Bonaldo, P., Chua, S., and Scherer, P.E. (2009). Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29, 1575-1591. https://doi.org/10.1128/MCB.01300-08
  49. Kim, D., Kim, J., Yoon, J.H., Ghim, J., Yea, K., Song, P., Park, S., Lee, A., Hong, C.P., Jang, M.S., et al. (2014). CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice. Diabetologia 57, 1456-1465. https://doi.org/10.1007/s00125-014-3237-5
  50. Ladanyi, A., Mukherjee, A., Kenny, H.A., Johnson, A., Mitra, A.K., Sundaresan, S., Nieman, K.M., Pascual, G., Benitah, S.A., Montag, A., et al. (2018). Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis. Oncogene 37, 2285-2301. https://doi.org/10.1038/s41388-017-0093-z
  51. Lau, M.F., Chua, K.H., Sabaratnam, V., and Kuppusamy, U.R. (2019). Rosiglitazone enhances the apoptotic effect of 5-fluorouracil in colorectal cancer cells with high-glucose-induced glutathione. Sci. Prog. 103, 36850419886448.
  52. Laurent, V., Guerard, A., Mazerolles, C., Le Gonidec, S., Toulet, A., Nieto, L., Zaidi, F., Majed, B., Garandeau, D., Socrier, Y., et al. (2016). Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity. Nat. Commun. 7, 10230. https://doi.org/10.1038/ncomms10230
  53. Lengyel, E., Makowski, L., DiGiovanni, J., and Kolonin, M.G. (2018). Cancer as a matter of fat: the crosstalk between adipose tissue and tumors. Trends Cancer 4, 374-384. https://doi.org/10.1016/j.trecan.2018.03.004
  54. Liang, W., Verschuren, L., Mulder, P., van der Hoorn, J.W., Verheij, J., van Dam, A.D., Boon, M.R., Princen, H.M., Havekes, L.M., Kleemann, R., et al. (2015). Salsalate attenuates diet induced non-alcoholic steatohepatitis in mice by decreasing lipogenic and inflammatory processes. Br. J. Pharmacol. 172, 5293-5305. https://doi.org/10.1111/bph.13315
  55. Madhusudan, S., Foster, M., Muthuramalingam, S.R., Braybrooke, J.P., Wilner, S., Kaur, K., Han, C., Hoare, S., Balkwill, F., Talbot, D.C., et al. (2004). A phase II study of etanercept (Enbrel), a tumor necrosis factor alpha inhibitor in patients with metastatic breast cancer. Clin. Cancer Res. 10, 6528-6534. https://doi.org/10.1158/1078-0432.CCR-04-0730
  56. Madke, B. and Khopkar, U. (2011). Nephrogenic systemic fibrosis. Indian Dermatol. Online J. 2, 51-56. https://doi.org/10.4103/2229-5178.85990
  57. Marcelin, G., Silveira, A.L.M., Martins, L.B., Ferreira, A.V.M., and Clement, K. (2019). Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis. J. Clin. Invest. 129, 4032-4040. https://doi.org/10.1172/JCI129192
  58. Nguyen, M.T., Favelyukis, S., Nguyen, A.K., Reichart, D., Scott, P.A., Jenn, A., Liu-Bryan, R., Glass, C.K., Neels, J.G., and Olefsky, J.M. (2007). A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNKdependent pathways. J. Biol. Chem. 282, 35279-35292. https://doi.org/10.1074/jbc.M706762200
  59. Nieman, K.M., Kenny, H.A., Penicka, C.V., Ladanyi, A., Buell-Gutbrod, R., Zillhardt, M.R., Romero, I.L., Carey, M.S., Mills, G.B., Hotamisligil, G.S., et al. (2011). Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med. 17, 1498-1503. https://doi.org/10.1038/nm.2492
  60. Okumura, T., Ohuchida, K., Sada, M., Abe, T., Endo, S., Koikawa, K., Iwamoto, C., Miura, D., Mizuuchi, Y., Moriyama, T., et al. (2017). Extrapancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells. Oncotarget 8, 18280-18295. https://doi.org/10.18632/oncotarget.15430
  61. Palanisamy, K., Nareshkumar, R.N., Sivagurunathan, S., Raman, R., Sulochana, K.N., and Chidambaram, S. (2019). Anti-angiogenic effect of adiponectin in human primary microvascular and macrovascular endothelial cells. Microvasc. Res. 122, 136-145. https://doi.org/10.1016/j.mvr.2018.08.002
  62. Pang, C., Gao, Z., Yin, J., Zhang, J., Jia, W., and Ye, J. (2008). Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity. Am. J. Physiol. Endocrinol. Metab. 295, E313-E322. https://doi.org/10.1152/ajpendo.90296.2008
  63. Panka, B.A., de Grooth, H.J., Spoelstra-de Man, A.M., Looney, M.R., and Tuinman, P.R. (2017). Prevention or treatment of Ards with aspirin: a review of preclinical models and meta-analysis of clinical studies. Shock 47, 13-21. https://doi.org/10.1097/SHK.0000000000000745
  64. Patsouris, D., Li, P.P., Thapar, D., Chapman, J., Olefsky, J.M., and Neels, J.G. (2008). Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 8, 301-309. https://doi.org/10.1016/j.cmet.2008.08.015
  65. Paz, G., Lim, E.L., Wong, M.L., and Licinio, J. (2011). Associations between adipokines and obesity-related cancer. Front. Biosci. (Landmark Ed.) 16, 1634-1650. https://doi.org/10.2741/3810
  66. Petrova, V., Annicchiarico-Petruzzelli, M., Melino, G., and Amelio, I. (2018). The hypoxic tumour microenvironment. Oncogenesis 7, 10. https://doi.org/10.1038/s41389-017-0011-9
  67. Pfeifer, E.C., Saxon, D.R., and Janson, R.W. (2017). Etanercept-induced hypoglycemia in a patient with psoriatic arthritis and diabetes. J. Investig. Med. High Impact Case Rep. 5, 2324709617727760.
  68. Quail, D.F. and Dannenberg, A.J. (2019). The obese adipose tissue microenvironment in cancer development and progression. Nat. Rev. Endocrinol. 15, 139-154. https://doi.org/10.1038/s41574-018-0126-x
  69. Quail, D.F. and Joyce, J.A. (2013). Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19, 1423-1437. https://doi.org/10.1038/nm.3394
  70. Quintanilla Rodriguez, B.S. and Correa, R. (2020). Rosiglitazone. In StatPearls [Internet], B. Abai, ed. (Treasure Island: StatPearls Publishing).
  71. Rangarajan, S., Bone, N.B., Zmijewska, A.A., Jiang, S., Park, D.W., Bernard, K., Locy, M.L., Ravi, S., Deshane, J., Mannon, R.B., et al. (2018). Metformin reverses established lung fibrosis in a bleomycin model. Nat. Med. 24, 1121-1127. https://doi.org/10.1038/s41591-018-0087-6
  72. Reguera-Nunez, E., Xu, P., Chow, A., Man, S., Hilberg, F., and Kerbel, R.S. (2019). Therapeutic impact of Nintedanib with paclitaxel and/or a PD-L1 antibody in preclinical models of orthotopic primary or metastatic triple negative breast cancer. J. Exp. Clin. Cancer Res. 38, 16. https://doi.org/10.1186/s13046-018-0999-5
  73. Reilly, S.M. and Saltiel, A.R. (2017). Adapting to obesity with adipose tissue inflammation. Nat. Rev. Endocrinol. 13, 633-643. https://doi.org/10.1038/nrendo.2017.90
  74. Rena, G., Hardie, D.G., and Pearson, E.R. (2017). The mechanisms of action of metformin. Diabetologia 60, 1577-1585. https://doi.org/10.1007/s00125-017-4342-z
  75. Rivera-Ortega, P., Hayton, C., Blaikley, J., Leonard, C., and Chaudhuri, N. (2018). Nintedanib in the management of idiopathic pulmonary fibrosis: clinical trial evidence and real-world experience. Ther. Adv. Respir. Dis. 12, 1753466618800618.
  76. Roma-Rodrigues, C., Mendes, R., Baptista, P.V., and Fernandes, A.R. (2019). Targeting tumor microenvironment for cancer therapy. Int. J. Mol. Sci. 20, 840. https://doi.org/10.3390/ijms20040840
  77. Romagnani, P., Annunziato, F., Lasagni, L., Lazzeri, E., Beltrame, C., Francalanci, M., Uguccioni, M., Galli, G., Cosmi, L., Maurenzig, L., et al. (2001). Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J. Clin. Invest. 107, 53-63. https://doi.org/10.1172/JCI9775
  78. Rossi, A., Latiano, T.P., Parente, P., Chiarazzo, C., Limosani, F., Di Maggio, G., and Maiello, E. (2017). The potential role of nintedanib in treating colorectal cancer. Expert Opin. Pharmacother. 18, 1153-1162. https://doi.org/10.1080/14656566.2017.1346086
  79. Russo, L. and Lumeng, C.N. (2018). Properties and functions of adipose tissue macrophages in obesity. Immunology 155, 407-417. https://doi.org/10.1111/imm.13002
  80. Sanchez-Martin, L., Estecha, A., Samaniego, R., Sanchez-Ramon, S., Vega, M.A., and Sanchez-Mateos, P. (2011). The chemokine CXCL12 regulates monocyte-macrophage differentiation and RUNX3 expression. Blood 117, 88-97. https://doi.org/10.1182/blood-2009-12-258186
  81. Saraei, P., Asadi, I., Kakar, M.A., and Moradi-Kor, N. (2019). The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances. Cancer Manag. Res. 11, 3295-3313. https://doi.org/10.2147/CMAR.S200059
  82. Scala, S. (2015). Molecular pathways: targeting the CXCR4-CXCL12 axis--untapped potential in the tumor microenvironment. Clin. Cancer Res. 21, 4278-4285. https://doi.org/10.1158/1078-0432.CCR-14-0914
  83. Seo, B.R., Bhardwaj, P., Choi, S., Gonzalez, J., Andresen Eguiluz, R.C., Wang, K., Mohanan, S., Morris, P.G., Du, B., Zhou, X.K., et al. (2015). Obesitydependent changes in interstitial ECM mechanics promote breast tumorigenesis. Sci. Transl. Med. 7, 301ra130. https://doi.org/10.1126/scitranslmed.3010467
  84. Sontake, V., Wang, Y., Kasam, R.K., Sinner, D., Reddy, G.B., Naren, A.P., McCormack, F.X., White, E.S., Jegga, A.G., and Madala, S.K. (2017). Hsp90 regulation of fibroblast activation in pulmonary fibrosis. JCI Insight 2, e91454.
  85. Stanley, T.L., Zanni, M.V., Johnsen, S., Rasheed, S., Makimura, H., Lee, H., Khor, V.K., Ahima, R.S., and Grinspoon, S.K. (2011). TNF- alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J. Clin. Endocrinol. Metab. 96, E146-E150. https://doi.org/10.1210/jc.2010-1170
  86. Sun, K., Tordjman, J., Clement, K., and Scherer, P.E. (2013). Fibrosis and adipose tissue dysfunction. Cell Metab. 18, 470-477. https://doi.org/10.1016/j.cmet.2013.06.016
  87. Talamantez-Lyburn, S., Brown, P., Hondrogiannis, N., Ratliff, J., Wicks, S.L., Nana, N., Zheng, Z., Rosenzweig, Z., Hondrogiannis, E., Devadas, M.S., et al. (2019). Gold nanoparticles loaded with cullin-5 DNA increase sensitivity to 17-AAG in cullin-5 deficient breast cancer cells. Int. J. Pharm. 564, 281-292. https://doi.org/10.1016/j.ijpharm.2019.04.022
  88. Thomas, D. and Apovian, C. (2017). Macrophage functions in lean and obese adipose tissue. Metabolism 72, 120-143. https://doi.org/10.1016/j.metabol.2017.04.005
  89. Tolios, A., De Las Rivas, J., Hovig, E., Trouillas, P., Scorilas, A., and Mohr, T. (2020). Computational approaches in cancer multidrug resistance research: Identification of potential biomarkers, drug targets and drugtarget interactions. Drug Resist. Updat. 48, 100662. https://doi.org/10.1016/j.drup.2019.100662
  90. Tougeron, D., Sha, D., Manthravadi, S., and Sinicrope, F.A. (2014). Aspirin and colorectal cancer: back to the future. Clin. Cancer Res. 20, 1087-1094. https://doi.org/10.1158/1078-0432.CCR-13-2563
  91. Varone, F., Sgalla, G., Iovene, B., Bruni, T., and Richeldi, L. (2018). Nintedanib for the treatment of idiopathic pulmonary fibrosis. Expert Opin. Pharmacother. 19, 167-175. https://doi.org/10.1080/14656566.2018.1425681
  92. Walker, C., Mojares, E., and Del Rio Hernandez, A. (2018). Role of extracellular matrix in development and cancer progression. Int. J. Mol. Sci. 19, 3028. https://doi.org/10.3390/ijms19103028
  93. Wang, C., Gao, C., Meng, K., Qiao, H., and Wang, Y. (2015). Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2. PLoS One 10, e0119348. https://doi.org/10.1371/journal.pone.0119348
  94. Wang, Z., Gao, J., Ohno, Y., Liu, H., and Xu, C. (2020). Rosiglitazone ameliorates senescence and promotes apoptosis in ovarian cancer induced by olaparib. Cancer Chemother. Pharmacol. 85, 273-284. https://doi.org/10.1007/s00280-019-04025-8
  95. Wei, Z., Zhao, D., Zhang, Y., Chen, Y., Zhang, S., Li, Q., Zeng, P., Li, X., Zhang, W., Duan, Y., et al. (2019). Rosiglitazone ameliorates bile duct ligationinduced liver fibrosis by down-regulating NF-kappaB-TNF-alpha signaling pathway in a PPARgamma-dependent manner. Biochem. Biophys. Res. Commun. 519, 854-860. https://doi.org/10.1016/j.bbrc.2019.09.084
  96. Weisberg, S.P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L., and Ferrante, A.W., Jr. (2003). Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796-1808. https://doi.org/10.1172/JCI200319246
  97. Wen, Y.A., Xing, X., Harris, J.W., Zaytseva, Y.Y., Mitov, M.I., Napier, D.L., Weiss, H.L., Mark Evers, B., and Gao, T. (2017). Adipocytes activate mitochondrial fatty acid oxidation and autophagy to promote tumor growth in colon cancer. Cell Death Dis. 8, e2593. https://doi.org/10.1038/cddis.2017.21
  98. Wu, X., Koh, G.Y., Huang, Y., Crott, J.W., Bronson, R.T., and Mason, J.B. (2019). The combination of curcumin and salsalate is superior to either agent alone in suppressing pro-cancerous molecular pathways and colorectal tumorigenesis in obese mice. Mol. Nutr. Food Res. 63, e1801097.
  99. Xing, F., Saidou, J., and Watabe, K. (2010). Cancer associated fibroblasts (CAFs) in tumor microenvironment. Front. Biosci. (Landmark Ed.) 15, 166-179. https://doi.org/10.2741/3613
  100. Xu, S., Xu, H., Wang, W., Li, S., Li, H., Li, T., Zhang, W., Yu, X., and Liu, L. (2019a). The role of collagen in cancer: from bench to bedside. J. Transl. Med. 17, 309. https://doi.org/10.1186/s12967-019-2058-1
  101. Xu, Y.Y., Liu, H., Su, L., Xu, N., Xu, D.H., Liu, H.Y., Spaner, D., Bed-David, Y., and Li, Y.J. (2019b). PPARgamma inhibits breast cancer progression by upregulating PTPRF expression. Eur. Rev. Med. Pharmacol. Sci. 23, 9965-9977.
  102. Yang, J., Zaman, M.M., Vlasakov, I., Roy, R., Huang, L., Martin, C.R., Freedman, S.D., Serhan, C.N., and Moses, M.A. (2019). Adipocytes promote ovarian cancer chemoresistance. Sci. Rep. 9, 13316. https://doi.org/10.1038/s41598-019-49649-1
  103. Yang, Y., Zhang, J., Gao, Q., Bo, J., and Ma, Z. (2017). Etanercept attenuates thermal and mechanical hyperalgesia induced by bone cancer. Exp. Ther. Med. 13, 2565-2569. https://doi.org/10.3892/etm.2017.4260
  104. Yao, Y., Xu, X.H., and Jin, L. (2019). Macrophage polarization in physiological and pathological pregnancy. Front. Immunol. 10, 792. https://doi.org/10.3389/fimmu.2019.00792
  105. Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.W., Karin, M., and Shoelson, S.E. (2001). Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293, 1673-1677. https://doi.org/10.1126/science.1061620
  106. Zhang, H.H., Souza, S.C., Muliro, K.V., Kraemer, F.B., Obin, M.S., and Greenberg, A.S. (2003). Lipase-selective functional domains of perilipin A differentially regulate constitutive and protein kinase A-stimulated lipolysis. J. Biol. Chem. 278, 51535-51542. https://doi.org/10.1074/jbc.M309591200
  107. Zhao, S., Mysler, E., and Moots, R.J. (2018). Etanercept for the treatment of rheumatoid arthritis. Immunotherapy 10, 433-445. https://doi.org/10.2217/imt-2017-0155
  108. Zhou, W., Guo, S., Liu, M., Burow, M.E., and Wang, G. (2019). Targeting CXCL12/CXCR4 axis in tumor immunotherapy. Curr. Med. Chem. 26, 3026-3041. https://doi.org/10.2174/0929867324666170830111531
  109. Zhou, Z.H., Ji, C.D., Xiao, H.L., Zhao, H.B., Cui, Y.H., and Bian, X.W. (2017). Reorganized collagen in the tumor microenvironment of gastric cancer and its association with prognosis. J. Cancer 8, 1466-1476. https://doi.org/10.7150/jca.18466

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