Влияние ожирения на развитие и прогрессию злокачественных новообразований: обзор современных данных и новых терапевтических мишеней

Влияние ожирения на развитие и прогрессию злокачественных новообразований: обзор современных данных и новых терапевтических мишеней

Автор: Семина Е.В., Данилова Н.В., Олейникова Н.А., Агапов М.А., Рубина К.А.

Журнал: Сибирский онкологический журнал @siboncoj

Рубрика: Обзоры

Статья в выпуске: 4 т.20, 2021 года.

Бесплатный доступ

Актуальность. Известно, что диабет 2-го типа, синдром обструктивного апноэ сна, остеоартроз и ряд злокачественных новообразований коррелируют с ожирением. Механизмы, обусловливающие взаимосвязь метаболических нарушений с возникновением злокачественных опухолей, пока неизвестны; значительную роль может играть изменение чувствительности к инсулину и факторам роста, изменение спектра секретируемых адипокинов или особенности их взаимодействия с рецепторами, изменение содержания стероидных половых гормонов в организме, а также особенности метаболизма глюкозы в опухолевых клетках (так называемый эффект Варбурга). Материал и методы. Проведен поиск источников, включая научные, клинические и обзорные статьи, опубликованные в рецензируемых журналах, индексируемых в pubmed, Wos, scopus и РИНЦ. Проанализировано более 150 статей, посвященных изучению взаимосвязи метаболических нарушений с опухолевой прогрессией, из которых 69 включены в данный обзор. Результаты. Основная стратегия лечения опухолевых заболеваний заключается в подавлении пролиферации опухолевых клеток и процессов метастазирования. Возможно, что значительную роль в этих процессах играет ряд факторов, способных усиливать побочные эффекты противоопухолевой терапии, поддерживать резистентность опухолевых клеток или изменять их метаболический профиль. Имеются новые данные о функции таких белков, как Т-кадгерин и рецептор урокиназы (upaR), и их возможном участии в регуляции метаболизма опухолевых клеток, в частности чувствительности к инсулину и гормонам жировой ткани. Помимо адипокинов как уже известных посредников, участвующих в канцерогенезе, в обзоре описаны новые данные о роли Т-кадгерина и урокиназного рецептора upaR в регуляции обменных процессов. Предложена модель, объясняющая взаимосвязь этих белков и метаболических нарушений, ассоциированных с процессами канцерогенеза и химиорезистентности опухолевых клеток. Заключение. Понимание факторов и механизмов, поддерживающих ожирение и нарушения метаболизма, с точки зрения их роли в канцерогенезе актуально как для разработки профилактических мер, так и для оптимизации терапевтических стратегий борьбы с опухолевыми заболеваниями.

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Метаболический синдром, ожирение, инсулин, инсулинорезистентность, адипонектин, Т-кадгерин, рецептор урокиназы

Короткий адрес: https://sciup.org/140254543

IDR: 140254543   |   DOI: 10.21294/1814-4861-2021-20-4-130-145

Список литературы Влияние ожирения на развитие и прогрессию злокачественных новообразований: обзор современных данных и новых терапевтических мишеней

  • Yunusova N.V., Kondakova I.V., Kolomiets L.A., Afanas'ev S.G., Kishkina A.Y., Spirina L.V. The role of metabolic syndrome variant in the malignant tumors progression. Diabetes Metab Syndr. 2018; 12(5): 807-812. https://doi.org/10.1016/j.dsx.2018.04.028.
  • Harvey I., Boudreau A., Stephens J.M. Adipose tissue in health and disease. Open Biol. 2020 Dec; 10(12): 200291. https://doi.org/10.1098/rsob.200291.
  • De Pergola G., Silvestris F. Obesity as a major risk factor for cancer. J Obes. 2013; 2013: 291546. https://doi.org/10.1155/2013/291546.
  • Amin M.N., Hussain M.S., Sarwar M.S., Rahman Moghal M.M., Das A., Hossain M.Z., Chowdhury J.A., Millat M.S., Islam M.S. How the association between obesity and inflammation may lead to insulin resistance and cancer. Diabetes Metab Syndr. 2019; 13(2): 1213-24. https://doi.org/10.1016/j.dsx.2019.01.041.
  • Ziemke F., Mantzoros C.S.Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr. 2010 Jan; 91(1): 258S-261S. https://doi.org/10.3945/ajcn.2009.28449C.
  • Porporato P.E. Understanding cachexia as a cancer metabolism syndrome. Oncogenesis. 2016 Feb 22; 5(2): e200. https://doi.org/10.1038/oncsis.2016.3.
  • Yoon Y.S., Kwon A.R., Lee Y.K., Oh S.W. Circulating adipokines and risk of obesity related cancers: A systematic review and meta-analysis. Obes Res Clin Pract. 2019 Jul-Aug; 13(4): 329-339. https://doi.org/10.1016/j.orcp.2019.03.006.
  • Rubio-Jurado B., Balderas-Peña L.M., García-Luna E.E., ZavalaCerna M.G., Riebeling-Navarro C., Reyes P.A., Nava-Zavala A.H. Obesity, Thrombotic Risk, and Inflammation in Cancer. Adv Clin Chem. 2018; 85: 71-89. https://doi.org/10.1016/bs.acc.2018.02.006.
  • Larsson S.C., Rutegård J., Bergkvist L., Wolk A. Physical activity, obesity, and risk of colon and rectal cancer in a cohort of Swedish men. Eur J Cancer. 2006 Oct; 42(15): 2590-7. https://doi.org/10.1016/j.ejca.2006.04.015.
  • Calle E.E., Rodriguez C., Walker-Thurmond K., Thun M.J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003; 348(17): 1625-38. https://doi.org/10.1056/NEJMoa021423.
  • Renehan A.G., Tyson M., Egger M., Heller R.F., Zwahlen M. Bodymass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008 Feb 16; 371(9612): 569-78. https://doi.org/10.1016/S0140-6736(08)60269-X.
  • Quail D.F., Dannenberg A.J. The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol. 2019 Mar; 15(3): 139-154. https://doi.org/10.1038/s41574-018-0126-x.
  • Bergan-Roller H.E., Sheridan M.A. The growth hormone signaling system: Insights into coordinating the anabolic and catabolic actions of growth hormone. Gen Comp Endocrinol. 2018; 258: 119-33. https://doi.org/10.1016/j.ygcen.2017.07.028.
  • Bauer T.W., Liu W., Fan F., Camp E.R., Yang A., Somcio R.J., Bucana C.D., Callahan J., Parry G.C., Evans D.B., Boyd D.D., Mazar A.P., Ellis L.M. Targeting of urokinase plasminogen activator receptor in human pancreatic carcinoma cells inhibits c-Met- and insulin-like growth factor-I receptor-mediated migration and invasion and orthotopic tumor growth in mice. Cancer Res. 2005 Sep 1; 65(17): 7775-81. https://doi.org/10.1158/0008-5472.CAN-05-0946.
  • Tsujimoto T., Kajio H., Sugiyama T. Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population-based observational study. Int J Cancer. 2017 Jul 1; 141(1): 102-111. https://doi.org/10.1002/ijc.30729.
  • Ahmed H.H., Hameed E.R.A., Shalby A.B. E.-N.H. Potent role of lipocalin in childhood obesity. World J Med Sci. 2012; 7(2): 100-4.
  • Di Zazzo E., Polito R., Bartollino S., Nigro E., Porcile C., Bianco A., Daniele A., Moncharmont B. Adiponectin as Link Factor between Adipose Tissue and Cancer. Int J Mol Sci. 2019 Feb 15; 20(4): 839. https://doi.org/10.3390/ijms20040839.
  • Karnati H.K., Panigrahi M.K., Li Y, Tweedie D., Greig N.H. Adiponectin as a Potential Therapeutic Target for Prostate Cancer. Curr Pharm Des. 2017; 23(28): 4170-4179. https://doi.org/10.2174/1381612823666170208123553.
  • Nunez N.P., Oh W.J., Rozenberg J., Perella C., Anver M., Barrett J.C., Perkins S.N., Berrigan D., Moitra J., Varticovski L., Hursting S.D., Vinson C. Accelerated tumor formation in a fatless mouse with type 2 diabetes and inflammation. Cancer Res. 2006 May 15; 66(10): 5469-76. https://doi.org/10.1158/0008-5472.CAN-05-4102.
  • Batista M.L.Jr., Olivan M., Alcantara P.S., Sandoval R., Peres S.B., Neves R.X., Silverio R., Maximiano L.F., Otoch J.P., Seelaender M. Adipose tissue-derived factors as potential biomarkers in cachectic cancer patients. Cytokine. 2013 Feb; 61(2): 532-9. https://doi.org/10.1016/j.cyto.2012.10.023.
  • Kyriakakis E., Frismantiene A., Dasen B., Pfaff D., Rivero O., Lesch K.P., Erne P., Resink T.J., Philippova M. T-cadherin promotes autophagy and survival in vascular smooth muscle cells through MEK1/2/Erk1/2 axis activation. Cell Signal. 2017 Jul; 35: 163-175. https://doi.org/10.1016/j.cellsig.2017.04.004.
  • Rubina K., Talovskaya E., Cherenkov V., Ivanov D., Stambolsky D., Storozhevykh T., Pinelis V., Shevelev A., Parfyonova Y., Resink T., Erne P., Tkachuk V. LDL induces intracellular signalling and cell migration via atypical LDL-binding protein T-cadherin. Mol Cell Biochem. 2005 May; 273(1-2): 33-41. https://doi.org/10.1007/s11010-005-0250-5.
  • Balatskaya M., Sharonov G., Baglay A., Balatskiy A. Tkachuk V. One receptor, two ligands, different responses: T-cadherin as a receptor for low density lipoprotein and adiponectin. FEBS J. 2017; 284: 102-403. https://doi.org/10.1111/febs.14174.
  • Shehzad A., Iqbal W., Shehzad O., Lee Y.S. Adiponectin: Regulation of its production and its role in human diseases. Hormones. 2012 Jan; 11(1): 8-20. https://doi.org/10.1007/BF03401534.
  • Parker-Duffen J.L., Nakamura K., Silver M., Kikuchi R., Tigges U., Yoshida S., Denzel M.S., Ranscht B., Walsh K. T-cadherin is essential for adiponectin-mediated revascularization. J Biol Chem. 2013 Aug 23; 288(34): 24886-97. https://doi.org/10.1074/jbc.M113.454835.
  • Rubina K., Kalinina N., Potekhina A., Efimenko A., Semina E., Poliakov A., Wilkinson D.G., Parfyonova Y., Tkachuk V. T-cadherin sup presses angiogenesis in vivo by inhibiting migration of endothelial cells. Angiogenesis. 2007; 10(3): 183-95. https://doi.org/10.1007/s10456-007-9072-2.
  • Rubina K.A., Surkova E.I., Semina E.V., Sysoeva V.Y., Kalinina N.I., Poliakov A.A., Treshalina H.M., Tkachuk V.A. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules. Cancers (Basel). 2015 Jul 21; 7(3): 1349-70. https://doi.org/10.3390/cancers7030840.
  • Hebbard L.W., Garlatti M., Young L.J., Cardiff R.D., Oshima R.G. Ranscht B. T-cadherin supports angiogenesis and adiponectin association with the vasculature in a mouse mammary tumor model. Cancer Res. 2008 Mar 1; 68(5): 1407-16. https://doi.org/10.1158/0008-5472.CAN-07-2953.
  • Andreeva A.V., Kutuzov M.A. Cadherin 13 in cancer. Genes Chromosomes Cancer. 2010 Sep; 49(9): 775-90. https://doi.org/10.1002/gcc.20787.
  • Rubina K.A., Sysoeva V.Y., Zagorujko E.I., Tsokolaeva Z.I., Kurdina M.I., Parfyonova Y.V., Tkachuk V.A. Increased expression of uPA, uPAR, and PAI-1 in psoriatic skin and in basal cell carcinomas. Arch Dermatol Res. 2017 Aug; 309(6): 433-442. https://doi.org/10.1007/s00403-017-1738-z.
  • Rubina K.A., Sysoeva V.Yu., Semina E.V., Yurlova E.I., Molochkov V.A., Khlebnikova A.N., Sedova T.G. Osobennosti ekspressii T-kadgerina v keratinotsitakh i sosudakh epitelial'nykh opukholei kozhi. Rossiiskii zhurnal kozhnykh i venericheskikh boleznei. 2013; 2013(1): 9-14.
  • McWilliam J., editor. Cadherins: Types, Structure and Functions. NY (USA): Nova Science Publishers; 2020. 171 p.
  • Duan B.S., Xie L.F., Wang Y. Aberrant Methylation of T-cadherin Can Be a Diagnostic Biomarker for Colorectal Cancer. Cancer Genomics Proteomics. 2017 Jul-Aug; 14(4): 277-284. https://doi.org/10.21873/cgp.20038.
  • Polito R., Nigro E., Fei L., DE Magistris L., Monaco M.L., D'Amico R., Naviglio S., Signoriello G., Daniele A. Adiponectin Is Inversely Associated With Tumour Grade in Colorectal Cancer Patients. Anticancer Res. 2020 Jul; 40(7): 3751-3757. https://doi.org/10.21873/anticanres.14364.
  • Nigro E., Schettino P., Polito R., Scudiero O., Monaco M.L., De Palma G.D., Daniele A. Adiponectin and colon cancer: evidence for inhibitory effects on viability and migration of human colorectal cell lines. Mol Cell Biochem. 2018 Nov; 448(1-2): 125-135. https://doi.org/10.1007/s11010-018-3319-7.
  • Tarkowski A., Bjersing J., Shestakov A., Bokarewa M.I. Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med. 2009 Sep; 14(6b): 1419-31. https://doi.org/10.1111/j.1582-4934.2009.00899.x.
  • Deshmukh S.K., Srivastava S.K., Zubair H., Bhardwaj A., Tyagi N., Al-Ghadhban A., Singh A.P., Dyess D.L., Carter J.E., Singh S. Resistin potentiates chemoresistance and stemness of breast cancer cells: Implications for racially disparate therapeutic outcomes. Cancer Lett. 2017 Jun 28; 396: 21-29. https://doi.org/10.1016/j.canlet.2017.03.010.
  • Assiri A.M., Kamel H.F., Hassanien M.F. Resistin, visfatin, adiponectin, and leptin: risk of breast cancer in pre- and postmenopausal saudi females and their possible diagnostic and predictive implications as novel biomarkers. Dis Markers. 2015; 2015: 253519. https://doi.org/10.1155/2015/253519.
  • Nakajima T.E., Yamada Y., Hamano T., Furuta K., Matsuda T., Fujita S., Kato K., Hamaguchi T., Shimada Y. Adipocytokines as new promising markers of colorectal tumors: adiponectin for colorectal adenoma, and resistin and visfatin for colorectal cancer. Cancer Sci. 2010 May; 101(5): 1286-91. https://doi.org/10.1111/j.1349-7006.2010.01518.x.
  • Demiray G., Değirmencioğlu S., Uğurlu E., Yaren A. Effects of Serum Leptin and Resistin Levels on Cancer Cachexia in Patients With Advanced-Stage Non-Small Cell Lung Cancer. Clin Med Insights Oncol. 2017 Feb 20; 11: 1179554917690144. https://doi.org/10.1177/1179554917690144.
  • Yaku K., Okabe K., Hikosaka K., Nakagawa T. NAD Metabolism in Cancer Therapeutics. Front Oncol. 2018 Dec 12; 8: 622. https://doi.org/10.3389/fonc.2018.00622.
  • Lin T.C. The role of visfatin in cancer proliferation, angiogenesis, metastasis, drug resistance and clinical prognosis. Cancer Manag Res. 2019 Apr 23; 11: 3481-3491. https://doi.org/10.2147/CMAR.S199597.
  • Silvério R., Lira F.S., Oyama L.M., Oller do Nascimento C.M., Otoch J.P., Alcântara P.S.M., Batista M.L.Jr., Seelaender M. Lipases and lipid droplet-associated protein expression in subcutaneous white adipose tissue of cachectic patients with cancer. Lipids Health Dis. 2017 Aug; 16(1): 159. https://doi.org/10.1186/s12944-017-0547-x.
  • Wysocka M.B., Pietraszek-Gremplewicz K., Nowak D. The Role of Apelin in Cardiovascular Diseases, Obesity and Cancer. Front Physiol. 2018 May 23; 9: 557. https://doi.org/10.3389/fphys.2018.00557.
  • Gourgue F., Mignion L., Van Hul M., Dehaen N., Bastien E., Payen V., Leroy B., Joudiou N., Vertommen D., Bouzin C., Delzenne N., Gallez B., Feron O., Jordan B.F., Cani P.D. Obesity and triple-negativebreast-cancer: Is apelin a new key target? J Cell Mol Med. 2020; 24(17): 10233-44. https://doi.org/10.1111/jcmm.15639.
  • Diakowska D., Markocka-Mączka K., Szelachowski P., Grabowski K. Serum levels of resistin, adiponectin, and apelin in gastroesophageal cancer patients. Dis Markers. 2014; 2014: 619649. https://doi.org/10.1155/2014/619649.
  • Goto H., Shimono Y., Funakoshi Y., Imamura Y., Toyoda M., Kiyota N., Kono S., Takao S., Mukohara T., Minami H. Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin. Oncogene. 2019; 38(6): 767-779. https://doi.org/10.1038/s41388-018-0477-8.
  • Liu Z., Xu J., He J., Liu H., Lin P., Wan X., Navone N.M, Tong Q., Kwak L.W., Orlowski R.Z., Yang J. Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation. Oncotarget. 2015 Oct 27; 6(33): 34329-41. https://doi.org/10.18632/oncotarget.6020.
  • Kato S., Abarzua-Catalan L., Trigo C., Delpiano A., Sanhueza C., García K., Ibañez C., Hormazábal K., Diaz D., Brañes J., Castellón E., Bravo E., Owen G., Cuello M.A. Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women. Oncotarget. 2015; 6(25): 21100-19. https://doi.org/10.18632/oncotarget.4228.
  • Zhou W., Tian Y., Gong H., Guo S., Luo C. Oncogenic role and therapeutic target of leptin signaling in colorectal cancer. Expert Opin Ther Targets. 2014 Aug; 18(8): 961-71. https://doi.org/10.1517/14728222.2014.926889.
  • Wu X., Yan Q., Zhang Z., Du G., Wan X. Acrp30 inhibits leptininduced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells. Oncol Rep. 2012 May; 27(5): 1488-96. https://doi.org/10.3892/or.2012.1670.
  • Kerem M., Ferahkose Z., Yilmaz U.T., Pasaoglu H., Ofluoglu E., Bedirli A., Salman B., Sahin T.T., Akin M. Adipokines and ghrelin in gastric cancer cachexia. World J Gastroenterol. 2008; 14(23): 3633-41. https://doi.org/10.3748/wjg.14.3633.
  • Huang Q., Fan Y.-Z., Ge B.-J., Zhu Q., Tu Z.-Y. Circulating Ghrelin in Patients with Gastric or Colorectal Cancer. Dig Dis Sci. 2007 Feb; 52(3): 803-9. https://doi.org/10.1007/s10620-006-9508-3.
  • Singhal M., Vishnu M.V.R., Raju S.V., Upadhyay Y. Interrelationship between obesity and cancer (A Review). Acad J Cancer Res. 2013; 6(1): 13-20. https://doi.org/10.5829/idosi.ajcr.2013.6.1.739.
  • Baglietto L., English D.R., Hopper J.L., MacInnis R.J., Morris H.A., Tilley W.D., Krishnan K., Giles G.G. Circulating steroid hormone concentrations in postmenopausal women in relation to body size and composition. Breast Cancer Res Treat. 2009 May; 115(1): 171-9. https://doi.org/10.1007/s10549-008-0069-3.
  • Brown S.B., Hankinson S.E. Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Steroids. 2015 Jul; 99(Pt A): 8-10. https://doi.org/10.1016/j.steroids.2014.12.013.
  • Noh H., Hong S., Huang S. Role of urokinase receptor in tumor progression and development. Theranostics. 2013 Jun; 3(7): 487-95. https://doi.org/10.7150/thno.4218.
  • Laurenzana A., Chillà A., Luciani C., Peppicelli S., Biagioni A., Bianchini F., Tenedini E., Torre E., Mocali A., Calorini L., Margheri F., Fibbi G., Del Rosso M. uPA/uPAR system activation drives a glycolytic phenotype in melanoma cells. Int J Cancer. 2017 Sep 15; 141(6): 1190-1200. https://doi.org/10.1002/ijc.30817.
  • Kubala M.H., DeClerck Y.A. The plasminogen activator inhibitor-1 paradox in cancer: a mechanistic understanding. Cancer Metastasis Rev. 2019 Sep; 38(3): 483-492. https://doi.org/10.1007/s10555-019-09806-4.
  • Mahmood N., Mihalcioiu C., Rabbani S.A. Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications. Front Oncol. 2018 Feb 12; 8: 24. https://doi.org/10.3389/fonc.2018.00024.
  • Guo Y., Mazar A.P., Lebrun J.J., Rabbani S.A. An antiangiogenic urokinase-derived peptide combined with tamoxifen decreases tumor growth and metastasis in a syngeneic model of breast cancer. Cancer Res. 2002 Aug 15; 62(16): 4678-84.
  • Danilova N.V., Mikhailov I.A., Oleinikova N.A., Mal'kov P.G., Chaika A.V., Khomyakov V.M., Kakotkin V.V., Yudin M.Yu. Persistentsiya antigenov virusa Epshteina-Barr pri rake zheludka: kharakteristika vospalitel'nykh kletochnykh reaktsii v opukholi. Arkhiv patologii. 2021; 83(1): 18-24. https://doi.org/10.17116/patol20218301118.
  • Deng T., Lyon C.J., Bergin S., Caligiuri M.A., Hsueh W.A. Obesity, Inflammation, and Cancer. Annu Rev Pathol. 2016 May 23; 11: 421-49. https://doi.org/10.1146/annurev-pathol-012615-044359.
  • Kahn C.R., Wang G., Lee K.Y. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest. 2019 Oct 1; 129(10): 3990-4000. https://doi.org/10.1172/JCI129187.
  • Il'yasova D., Colbert L.H., Harris T.B., Newman A.B., Bauer D.C., Satterfield S., Kritchevsky S.B. Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev. 2005 Oct; 14(10): 2413-8. https://doi.org/10.1158/1055-9965.EPI-05-0316.
  • Zhang X., Liu S., Zhou Y. Circulating levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α and risk of colorectal adenomas: a meta-analysis. Oncotarget. 2016; 7(39): 64371-79. https://doi.org/10.18632/oncotarget.11853.
  • Semina E.V., Rubina K.A., Shmakova A.A., Rysenkova K.D., Klimovich P.S., Aleksanrushkina N.A., Sysoeva V.Y., Karagyaur M.N., Tkachuk V.A. Downregulation of uPAR promotes urokinase translocation into the nucleus and epithelial to mesenchymal transition in neuroblastoma. J Cell Physiol. 2020 Sep; 235(9): 6268-6286. https://doi.org/10.1002/jcp.29555.
  • Pliyev B.K. Activated human neutrophils rapidly release the chemotactically active D2D3 form of the urokinase-type plasminogen activator receptor (uPAR/CD87). Mol Cell Biochem. 2009 Jan; 321(1-2): 111-22. https://doi.org/10.1007/s11010-008-9925-z.
  • Cabral-Pacheco G.A., Garza-Veloz I., Castruita-De la Rosa C., Ramirez-Acuña J.M., Perez-Romero B.A., Guerrero-Rodriguez J.F., Martinez-Avila N., Martinez-Fierro M.L. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2020 Dec 20; 21(24): 9739. https://doi.org/10.3390/ijms21249739
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