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The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer

DOI: 10.3390/ijms131013240

Keywords: matrix metalloproteinase, tissue inhibitor of matrix metalloproteinase, colorectal cancer, adenoma, tumor progression, invasion, metastasis, prognosis, biomarker

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Abstract:

Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are especially important in the process of tumor invasion, progression and the metastasis of colorectal cancer (CRC). It has been proposed that MMPs and TIMPs might play a part not only in tumor invasion and initiation of metastasis but also in carcinogenesis from colorectal adenomas. Several recent studies demonstrated that high preoperative serum or plasma MMP-2, MMP-9 and TIMP-1 antigen levels are strong predictive factors for poor prognosis in patients with CRC and their determination might be useful for identification of patients with higher risk for cancer recurrence. MMP-9 and TIMP-1 have significant potential tumor marker impact in CRC. Their diagnostic sensitivity is consistently higher than those of conventional biomarkers. The pharmacological targeting of CRC by the development of a new generation of selective inhibitors of MMPs, that is highly specific for certain MMPs, is a promising and challenging area for the future.

References

[1]  Ferlay, J.; Parkin, D.M.; Steliarova-Fiocher, E. Estimates of cancer incidence and mortality in Europe in 2008. Eur. J. Cancer 2010, 46, 765–781.
[2]  Siegel, R.; Desantis, C.; Virgo, K.; Stein, K.; Mariotto, A.; Smith, T.; Cooper, D.; Gansler, T.; Lerro, C.; Fedewa, S.; et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J. Clin 2012, 62, 220–241.
[3]  Moghimi-Dehkodri, B.; Safaee, A. An overview of colorectal cancer survival rates and prognosis in Asia. World J. Gastrointest. Oncol 2012, 4, 71–75.
[4]  Wittmann, T.; Stockbrugger, R.; Herszényi, L.; Jonkers, D.; Molnár, B.; Saurin, J.C.; Regula, J.; Malesci, A.; Laghi, L.; Pintér, T.; et al. New European initiatives in colorectal cancer screening: Budapest Declaration. Dig. Dis 2012, 30, 320–322.
[5]  Hart, I.R.; Saini, A. Biology of tumour metastasis. Lancet 1992, 339, 1453–1457.
[6]  Nigam, A.K.; Pignatelli, M.; Boulos, P. Current concepts in metastasis. Gut 1994, 35, 996–1000.
[7]  Herszényi, L.; Plebani, M.; Carraro, P.; de Paoli, M.; Roveroni, G.; Cardin, R.; Foschia, F.; Tulassay, Z.; Naccarato, R.; Farinati, F. Proteases in gastrointestinal neoplastic disease. Clin. Chim. Acta 2000, 291, 171–187.
[8]  Hoon, D.S.; Ferris, R.; Tanaka, R.; Chong, K.K.; Alix-Panabiéres, C.; Pantel, K. Molecular mechanisms of metastasis. J. Surg. Oncol 2011, 103, 508–517.
[9]  Witte, M.H.; Dellinger, M.T.; McDonald, D.M.; Nathanson, S.D.; Boccardo, F.M.; Campisi, C.C.; Sleeman, J.P.; Gershenwald, J.E. Lymphangiogenesis and hemangiogenesis: Potential targets for therapy. J. Surg. Oncol 2011, 103, 489–500.
[10]  Herszényi, L.; Lakatos, G.; Hritz, I.; Varga, M.Z.; Cierny, G.; Tulassay, Z. The role of inflammation and proteinases in tumor progression. Dig. Dis 2012, 30, 249–254.
[11]  Yurchenko, P.D.; Schittny, J.C. Molecular architecture of basement membrane. FABES J 1990, 4, 1577–1590.
[12]  DeClerck, Y.A.; Mercurio, A.M.; Stack, M.S.; Chapman, H.A.; Zutter, M.M.; Muschel, R.J.; Raz, A.; Matrisian, L.M.; Sloane, B.F.; Noel, A.; et al. Proteases, extracellular matrix and cancer: A workshop of the path B study section. Am. J. Pathol 2004, 164, 1131–1139.
[13]  Cavallo-Medved, D.; Rudy, D.; Blum, G.; Bogyo, M.; Caglic, D.; Sloane, B.F. Live-cell imaging demonstrates extracellular matrix degradation in association with active cathepsin B in caveolas of endothelial cells during tube formation. Exp. Cell Res 2009, 315, 1234–1246.
[14]  Liotta, L.A.; Kohn, E.C. The microenvironment of the tumour-host interface. Nature 2001, 411, 375–379.
[15]  Geho, D.H.; Bandle, R.W.; Clair, T.; Liotta, L.A. Physiological mechanisms of tumor-cell invasion and migration. Physiology (Bethesda) 2005, 20, 194–200.
[16]  Mantovani, A.; Allavena, P.; Sica, A; Balkwill, F. Cancer-related inflammation. Nature 2008, 454, 436–444.
[17]  Balkwill, F.; Mantovani, A. Inflammation and cancer: Back to Virchow? Lancet 2001, 357, 539–545.
[18]  Hold, G.L.; El-Omar, M.E. Genetic aspects of inflammation and cancer. Biochem. J 2008, 40, 225–235.
[19]  Mantovani, A.; Garlanda, C.; Allavena, P. Molecular pathways and targets in cancer-related inflammation. Ann. Med 2010, 42, 161–170.
[20]  Colotta, F.; Allavena, P.; Sica, A.; Garlanda, C.; Mantovani, A. Cancer-related inflammation, the seventh hallmark of cancer: Links to genetic instability. Carcinogenesis 2009, 7, 1073–1081.
[21]  Maltzki, C.; Emmrich, J. Inflammation and immunity in the tumor environment. Dig. Dis 2010, 28, 574–578.
[22]  Grivennikov, S.I.; Karin, M. Inflammatory cytokines in cancer: Tumour necrosis factor and interleukin 6 take the stage. Ann. Rheum. Dis 2011, 70, i104–i108.
[23]  Bromberg, J.; Wang, T.C. Inflammation and cancer: IL-6 and STAT3 completes the link. Cancer Cell 2009, 15, 79–80.
[24]  Scheede-Bergdahl, C.; Watt, H.L.; Trutschnigg, B.; Kilgour, R.D.; Haggarty, A.; Lucar, E.; Vigano, A. Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer cachexia? Clin. Nutr 2012, 31, 85–88.
[25]  Burney, B.O.; Hayes, T.G.; Smiechowska, J.; Cardwell, G.; Papusha, V.; Bhargava, P.; Konda, B.; Auchus, R.J.; Garcia, J.M. Low testosterone levels and increased inflammatory markers in patients with cancer and relationship with cachexia. J. Clin. Endocrinol. Metab 2012, 97, E700–E709.
[26]  Liotta, L.A.; Stetler-Stevenson, W.G. Tumor invasion and metastasis: An imbalance of positive and negative regulation. Cancer Res 1991, 51, 5054–5059.
[27]  Dass, K.; Ahmad, A.; Azmi, A.S.; Sarkar, S.H.; Sarkar, F.H. Evolving role of uPA/uPAR system in human cancers. Cancer Treatment Rev 2008, 34, 122–136.
[28]  Polgar, L. Common feature of the four types of protease mechanisms. Biol. Chem. Hoppe-Seyler 1990, 371, 327–331.
[29]  Plebani, M.; Herszényi, L.; Cardin, R.; Roveroni, G.; Carraro, P.; de Paoli, M.; Rugge, M.; Grigioni, W.F; Nitti, D.; Naccarato, R.; et al. Cysteine and serine proteases in gastric cancer. Cancer 1995, 76, 367–375.
[30]  Herszényi, L.; Plebani, M.; Carraro, P.; de Paoli, M.; Roveroni, G.; Cardin, R.; Tulassay, Z.; Naccarato, R.; Farinati, F. The role of cysteine and serine proteases in colorectal cancer. Cancer 1999, 86, 1135–1142.
[31]  Herszényi, L.; Farinati, F.; Cardin, R.; István, G.; Molnár, L.D.; Hritz, I.; de Paoli, M.; Plebani, M.; Tulassay, Z. Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer. BMC Cancer 2008, 8, 194.
[32]  Herszényi, L.; Plebani, M.; Carraro, P.; de Paoli, M.; Cardion, R.; di Mari, F.; Kusstacher, S.; Naccarato, R.; Farinati, F. Impaired fibrinolysis and increased protease levels in gastric and duodenal mucosa of patients with active duodenal ulcer. Am. J. Gastroenterol 1997, 92, 843–847.
[33]  Herszényi, L.; István, G.; Cardin, R.; de Paoli, M.; Plebani, M.; Tulassaay, Z.; Farinati, F. Serum cathepsin B and plasma urokinase-type plasminogen activator levels in gastrointestinal tract cancers. Eur. J. Cancer Prev 2008, 17, 438–445.
[34]  Van Kempelen, L.C.L.; de Visser, K.A.; Coussens, L.M. Inflammation, proteases and cancer. Eur. J. Cancer 2006, 42, 728–734.
[35]  Affara, N.I.; Andreau, P.; Coussens, L.M. Delineating protease functions during cancer development. Methods Mol. Biol 2009, 539, 1–32.
[36]  Noel, A.; Jost, M.; Maquoi, E. Matrix metalloproteinases at cancer tumor-host interface. Semin. Cell Dev. Biol 2008, 19, 52–60.
[37]  Kessenbrock, K.; Plaks, V.; Werb, Z. Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell 2010, 141, 52–67.
[38]  Page-McCaw, A.; Ewald, A.J.; Werb, Z. Matrix metalloproteinases and the regulation of tissue remodeling. Nat. Rev. Mol. Cell Biol 2007, 8, 221–233.
[39]  Hayden, D.M.; Forsyth, C.; Keshavarzian, A. the role of matrix metalloproteinases in intestinal epithelial wound healing during normal and inflammatory states. J. Surg. Res 2011, 168, 315–324.
[40]  Puthenedam, M.; Wu, F.; Shetye, A.; Michaels, A.; Rhee, K.J.; Kwon, J.H. Matrilysin (MMP7) cleaves gelactin-3 and inhibits wound healing in intestinal epithelial cells. Inflamm. Bowel Dis 2011, 17, 260–267.
[41]  Sun, J. Matrix metalloproteinases and tissue inhibitor of metalloproteinase are essential for the inflammatory response in cancer cells. J. Signal Transduct 2010, 2010, 985132.
[42]  Herszényi, L.; Hritz, I.; Pregun, I.; Sipos, F.; Juhasz, M.; Molnar, B.; Tulassay, Z. Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in the esophageal carcinogenesis. World J. Gastroenterol 2007, 13, 676–682.
[43]  Herszényi, L.; Sipos, F.; Galamb, O.; Solymosi, N.; Hritz, I.; Miheller, P.; Berczi, L.; Molnár, B.; Tulassay, Z. Matrix metalloproteinase-9 expression in the normal mucosa-adenoma-dysplasiaadenocarcinoma sequence of the colon. Pathol. Oncol. Res 2008, 14, 31–37.
[44]  Jensen, S.A.; Vainer, B.; Bartels, A.; Brünner, M.; S?rensen, J.B. Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells—Associations with histopathology and patients outcome. Eur. J. Cancer 2010, 46, 3233–3242.
[45]  Kirkegaard, T.; Hansen, A.; Bruun, E.; Brynskov, J. Expression and localization of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn’s disease. Gut 2004, 53, 701–709.
[46]  Stallmach, A.; Chan, C.C.; Ecker, K.W.; Feifel, G.; Herbst, H; Schuppan, D.; Zeitz, M. Comparable expression of matrix metalloproteinases 1 and 2 in pouchitis and ulcerative colitis. Gut 2000, 47, 415–422.
[47]  Von Lampe, B.; Barthel, B.; Coupland, S.E.; Riecken, E.O.; Rosewicz, S. Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. Gut 2000, 47, 63–73.
[48]  Ravi, A.; Garg, P.; Sitaraman, S.V. Matrix metalloproteinases in inflammatory bowel disease: Boon or a baine? Inflamm. Bowel Dis 2007, 13, 97–107.
[49]  Lakatos, G.; Sipos, F.; Miheller, P.; Hritz, I.; Varga, M.Z.; Juhász, M.; Molnár, B.; Tulassay, Z.; Herszényi, L. The behavior of matrix metalloproteinase-9 in lymphocytic colitis, collagenous colitis and ulcerative colitis. Pathol. Oncol. Res 2012, 18, 85–91.
[50]  Lakatos, G.; Hritz, I.; Varga, M.Z.; Juhász, M.; Miheller, P.; Cierny, G.; Tulassay, Z.; Herszényi, L. The impact of matrix metalloproteinases and their tissue inhibitors in inflammatory bowel diseases. Dig. Dis 2012, 30, 289–295.
[51]  Mashhadiabbas, F.; Mahjour, F.; Mahjour, S.B.; Fereidooni, F.; Hosseini, F.S. The immunohistochemical characterization of MMP-2, MMP-10, TIMP-1, TIMP-2 and podoplanin in oral squamous cell carcinoma. Oral Surg. Oral Med. Pathol. Oral Radiol 2012, 114, 240–250.
[52]  Fullár, A.; Kovalszky, I.; Bitsche, M.; Romani, A.; Schartinger, V.H.; Sprinzl, G.M.; Riechelmann, H.; Dudás, J. Tumor cell and carcinoma-associated fibroblast interaction regulates matrix metalloproteinases ant their inhibitors in oral squamous cell carcinoma. Exp. Cell Res 2012, 318, 1517–1527.
[53]  Roomi, M.W.; Kalinovsky, T.; Rath, M.; Niedzwiecki, A. Down-regulation of urokinase plasminogen activator and matrix metalloproteinases and up-regulation of their inhibitors by a novel nutrient mixture in human prostate cancer cell lines PC-3 and DU-145. Oncol. Rep 2011, 26, 1407–1413.
[54]  Figueira, R.C.; Gomes, L.R.; Neto, J.S.; Silva, F.C.; Silva, I.D.; Sogayar, M.C. Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential. BMC Cancer 2009, 9, 20.
[55]  Roomi, M.W.; Monterrey, J.C.; Kalinovsky, T.; Rath, M.; Niedzwiecki, A. In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines, inducers and inhibitors. Oncol. Rep 2010, 223, 605–614.
[56]  Hu, X.; Li, D.; Zhang, W.; Zhou, J.; Tang, B.; Li, L. Matrix metalloproteinase-9 expression correlates with prognosis and involved in ovarian cancer cell invasion. Arch. Gynecol. Obstet 2012, doi:10.1007/s00404-012-2456-6.
[57]  Roomi, M.W.; Kalniovsky, T.; Rath, M.; Niedzwiecki, A. Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines. Oncol. Rep 2012, 28, 768–776.
[58]  Sharma, R.; Chattopadhyay, T.K.; Mathur, M.; Ralhan, R. Prognostic significance of stromelysin-2 and tissue inhibitor of matrix metalloproteinase-2 in esophageal cancer. Oncology 2004, 67, 300–309.
[59]  Groblewska, M.; Siewko, M.; Mroczko, B.; Szmitkowski, M. The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer. Folia Histochem. Cytobiol 2012, 50, 12–19.
[60]  Salmela, M.T.; Karjalainen-Lindsberg, M.L.; Puolakkainen, P.; Saarialho-Kere, U. Upregulation and differential expression of matrilysin (MMP-7) and metalloelastase (MMP-12) and their inhibitors TIMP-1 and TIMP-3 in Barrett’s oesophageal adenocarcinoma. Br. J. Cancer 2001, 85, 383–392.
[61]  Lukaszewicz-Zajac, M.; Mroczko, B.; Szmitkowski, M. Gastric cancer—The role of matrix metalloproteinases in tumor progression. Clin. Chim. Acta 2011, 412, 1725–1730.
[62]  Liu, H.Q.; Song, S.; Wang, J.H.; Zhang, S.L. Expression of MMP-3 and TIMP-3 in gastric cancer tissue and its clinical significance. Oncol. Lett 2011, 2, 1319–1322.
[63]  Joergensen, M.T.; Brünner, N.; de Muckadell, O.B. comparison of circulating MMP-9, TIMP-1 and CA-19-9 in the detection of pancreatic cancer. Anticancer Res 2010, 30, 587–592.
[64]  Giannopoulos, G.; Pavlakis, K.; Parasi, A.; Kavatzas, N.; Tiniakos, D.; Karakosta, A.; Tzanakis, N.; Peros, G. The expression of matrix metalloproteinase-2 and -9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters. Anticancer Res 2008, 28, 1875–1881.
[65]  Gao, Z.H.; Tretiakova, M.S.; Liu, W.H.; Gong, C.; Farris, P.D.; Hart, J. Association of E-cadherin, matrix metalloproteinases with the progression and metastasis of hepatocellular carcinoma. Mod. Pathol 2006, 19, 533–540.
[66]  Tretiakova, M.S.; Hart, J.; Shabani-Rad, M.T.; Zhang, J.; Gao, Z.H. Distinction of hepatocellular adenoma from hepatocellular carcinoma with and without cirrhosis using E-cadherin and matrix metalloproteinase immunohistochemistry. Mod. Pathol 2009, 22, 1113–1120.
[67]  Roy, R.; Yang, J.; Moses, A.M. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J. Clin. Oncol 2009, 27, 5287–5297.
[68]  Yeh, Y.C.; Sheu, B.S.; Cheng, H.C.; Wang, Y.L.; Yang, H.B.; Wu, J.J. Elevated matrix metalloproteinase-3 and -7 in H. pylori-related gastric cancer can be biomarkers correlating with a poor survival. Dig. Dis. Sci 2010, 55, 1649–1657.
[69]  Medina, C.; Radomski, M.W. Role of matrix metalloproteinases in intestinal inflammation. J. Pharmacol. Exp. Ther 2006, 318, 933–938.
[70]  Wiercinska-Drapalo, A.; Jaroszewicz, J.; Flisiak, R.; Prokopowicz, D. Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity. World J. Gastroenterol 2003, 9, 2843–2845.
[71]  Meijer, M.J.; Mieremet-Ooms, M.A.; van Hogezand, R.A.; Lamers, C.B.; Hommes, D.W.; Verspaget, H.W. Role of matrix metalloproteinase, tissue inhibitor of matrix metalloproteinase and tumor necrosis factor-alpha single nucleotide gene polymorphisms in inflammatory bowel disease. World J. Gastroenterol 2007, 13, 2960–2966.
[72]  Meijer, M.J.; Mieremet-Ooms, M.A.; Sier, C.F.; van Hogezand, R.A.; Lamers, C.B.; Hommes, D.W.; Verspaget, H.W. Matrix metalloproteinases and their tissue inhibitors as prognostic indicators for diagnostic and surgical recurrence in Crohn’s disease. Inflamm. Bowel Dis 2009, 15, 84–92.
[73]  Kapsoritakis, A.N.; Kapsoritaki, A.L.; Davidi, I.P.; Lotis, V.D.; Manolakis, A.C.; Mylonis, P.I.; Theodoridou, A.T.; Germenis, A.E.; Potamianos, S.P. Imbalance of tissue inhibitors of metalloproteinases (TIMP) -1 and -4 serum levels in patients with inflammatory bowel disease. BMC Gastroenterol 2008, 8, 55.
[74]  M?kitalo, L.; Kolho, K.L.; Karikoski, R.; Anthoni, H.; Saarialho-Kere, U. Expression profiles of matrix metalloproteinases and their inhibitors in colonic inflammation related to pediatric inflammatory bowel disease. Scan. J. Gastroenterol 2010, 45, 862–871.
[75]  Hornebeck, W.; Lambert, E.; Petitfrére, E.; Bernard, P. Beneficial and detrimental influences of tissue inhibitor of metalloproteinase-1 (TIMP-1) in tumor progression. Biochimie 2005, 87, 377–383.
[76]  Schr?tzlmair, F.; Kopitz, C.; H?lbgewachs, B.; Lu, F.; Algül, H.; Brünner, N.; Gansbacher, B.; Krüger, A. Tissue inhibitor of metalloproteinase-1-induced scattered liver metastasis is mediated by host-derived urokinase-type plasminogen activator. J. Cell Mol. Med 2010, 14, 2760–2770.
[77]  Schelter, F.; Halbgewachs, B.; B?umleer, P.; Neu, C.; G?rlach, A.; Schr?tzlmair, F.; Krüger, A. Tissue inhibitor of metalloproteinase-1-induced scattered liver metastasis is mediated by hypoxia-inducible factor-1α. Clin. Exp. Metastasis 2011, 28, 91–99.
[78]  Stetler-Stevenson, W.G. The tumor microenvironment: Regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2. Cancer Metastasis Rev 2008, 27, 57–66.
[79]  Bourboulia, D.; Stetler-Stevenson, W.G. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Semin. Cancer Biol 2010, 20, 161–168.
[80]  Lambert, E.; Dassé, E.; Haye, B.; Petitfére, E. TIMPs as multifactorial proteins. Crit. Rev. Oncol. Hematol 2004, 49, 187–198.
[81]  Kallio, J.P.; Hopkins-Donaldson, S.; Baker, A.H.; K?h?ri, V.M. TIMP-3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway. Int. J. Cancer 2011, 128, 991–996.
[82]  Fernández, C.A.; Moses, M.A. Modulation of angiogenesis by tissue inhibitor of metalloproteinase-4. Biochem. Biphys. Res. Commun 2006, 345, 523–529.
[83]  Dao Thi, M.U.; Trocmé, C.; Montmasson, M.P.; Fanchon, E.; Toussaint, B.; Tracqui, P. Investigating metalloproteinases MMP-2 and MMP-9 mechanosensitivity to feedback loops involved in the regulation of in vitro angiogenesis by endogenous mechanical stresses. Acta Biother 2012, 60, 21–40.
[84]  Lamoreaux, W.J.; Fitzgerald, M.E.; Reiner, A.; Hasty, K.A.; Charles, S.T. Vascular endothelial growth factor increases release of gelatinase A and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cellsin vitro. Microvasc. Res 1998, 55, 29–42.
[85]  Carmeliet, P.; Jain, R.K. Angiogenesis in cancer and other diseases. Nature 2000, 407, 249–257.
[86]  Lee, M.S.; Jung, J.I.; Kwon, S.H.; Lee, S.M.; Morita, K.; Her, S. TIMP-2 fusion protein with human serum albumin potentiates anti-angiogenesis-mediated inhibition of tumor growth by suppressing MMP-2 expression. PLoS One 2012, 7, e35710.
[87]  Zeng, Z.S.; Huang, Y.; Cohen, A.M.; Guillem, J.G. Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J. Clin. Oncol 1996, 14, 3133–3140.
[88]  Guzinska-Ustymovicz, K. MMP-9 and cathepsin B expression in tumor budding as an indicator of a more aggressive phenotype of colorectal cancer. Anticancer Res 2006, 26, 1589–1594.
[89]  Curran, S.; Dundas, S.R.; Buxton, J.; Leeman, M.F.; Ramsay, R.; Murray, G.I. Matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. Clin. Cancer Res 2004, 10, 8229–8234.
[90]  Lyall, M.S.; Dundas, S.R.; Curran, S.; Murray, G.I. Profiling markers of prognosis in colorectal cancer. Clin. Cancer Res 2006, 12, 1184–1191.
[91]  Bendardaf, R.; Buhmeida, A.; Hilska, M.; Laato, M.; Syrj?nen, S.; Collan, Y.; Pyrh?nen, S. MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients. Cancer Invest 2010, 1, 38–43.
[92]  Buhmeida, A.; Bendardaf, R.; Hilska, M.; Collan, Y.; Laato, M.; Syrynen, S.; Syrjanen, K.; Pyrh?nen, S. Prognostic significance of matrix metalloproteinase-9 (MMP-9) in stage II colorectal cancer. J. Gastrointest. Cancer 2009, 40, 91–97.
[93]  Chu, D.; Zhao, Z.; Li, Y.; Zheng, J.; Zhao, Q.; Wang, W. Matrix metalloproteinase-9 is associated with relapse and prognosis of patients with colorectal cancer. Ann. Surg. Oncol 2012, 19, 318–325.
[94]  Langers, A.M.J.; Verspaget, H.W.; Hawinkels, L.J.A.C.; Kubben, F.J.G.M.; van Duijn, W.; van der Reijden, J.J.; Hardwick, J.C.H.; Hommes, D.W.; Sier, C.F.M. MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients. Br. J. Cancer 2012, 106, 1495–1498.
[95]  Hilska, M.; Roberts, P.J.; Collan, Y.U.; Laine, O.; K?ssi, J.; Hirsimaki, P.; Rahkonen, O.; Laato, M. Prognostic significance of matrix metalloproteinase-1, -2, -7 and -13 and tissue inhibitors of metalloproteinases -1, -2 -3 and-4 in colorectal cancer. Int. J. Cancer 2007, 121, 714–723.
[96]  Kim, Y.W.; Ko, Y.T.; Kim, N.K.; Chung, H.C.; Min, B.S.; Lee, K.Y.; Park, J.P.; Kim, H. A comparative study of protein expression in primary colorectal cancer and synchronous hepatic metastases: The significance of matrix metalloproteinase-1 expression as a predictor of liver metastasis. Scand. J. Gastroenterol 2010, 45, 217–225.
[97]  M?ller S?rensen, N.; Wejgaard S?rensen, I.; ?rnbjerg Würtz, S.; Schrohol, A.S.; Dowell, B.; Davis, G.; Jarle Christensen, I.; Nielsen, H.J.; Brünner, N. Biology and potential clinical implications of tissue inhibitor of metalloproteinase-1 in colorectal cancer treatment. Scand. J. Gastroenterol 2008, 43, 774–786.
[98]  Gonzáles, L.; Eiró, N.; Gonzáles, L.O.; Andicoechea, A.; Barbón, E.; Garcia-Muniz, J.L.; Vizozo, F.J. Effect of the expression of matrix metalloproteases and their tissue inhibitors on survival of patients with resectable colorectal cancer. Dig. Dis. Sci 2012, 57, 2063–2071.
[99]  Konishi, K.; Fujii, T.; Boku, N.; Kato, S.; Koba, I.; Ohtsu, A.; Tajiri, H.; Ochiai, A.; Yoshida, S. Clinicopathological differences between colonic and rectal carcinomas: Are they based on the same mechanism of carcinogenesis? Gut 1999, 45, 818–821.
[100]  Kapitejin, E.; Liefers, G.J.; Los, L.C.; Kranenbarg, E.K.; Hermans, J.; Tollenaar, R.A.; Moriya, Y.; Velde, C.J.H.; Krieken, J.H. Mechanisms of oncogenesis in colon versus rectal cancer. J. Pathol 2001, 195, 171–178.
[101]  Svagzdys, S.; Lesauskaite, V.; Pangonyte, D.; Saladzinskas, Z.; Tamelis, A.; Pavalkis, D. Matrix metalloproteinase-9 is a prognostic marker to predict survival of patients who underwent surgery due to rectal carcinoma. Tohoku J. Exp. Med 2011, 223, 67–73.
[102]  Cavdar, Z.; Canda, A.E.; Terzi, C.; Sarioglu, S.; Fuzun, M.; Oktay, G. Role of gelatinases (matrix metalloproteinases 2 and 9) vascular endothelial growth factor and endostatin on clinicopathological behaviour of rectal cancer. Colorectal Dis 2011, 13, 154–160.
[103]  Tomita, T.; Iwata, K. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in colonic adenomas-adenocarcinomas. Dig. Colon. Rectum 1996, 39, 1255–1264.
[104]  Liabakk, N.B.; Talbot, J.; Wilkinson, K.; Balkwill, F. Matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) type IV collagenase in colorectal cancer. Cancer Res 1996, 56, 190–196.
[105]  Takeuchi, T.; Hisanaga, M.; Nagao, M.; Ikeda, N.; Fujii, H.; Koyama, F.; Mukowaga, T.; Matsumoto, H.; Kondo, S.; Takahashi, C.; et al. The membrane-anchored matrix metalloproteinase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator for colorectal cancer. Clin. Cancer Res 2004, 10, 5572–5579.
[106]  Gimeno-Garcia, A.Z.; Sanatana-Rodriguez, A.; Jiménez, A.; Parra-Blanco, A.; Nicolás-Pérez, D.; Puz-Cabrera, C.; Diaz-Gonazález, F.; Median, C.; Diaz-Flores, L.; Quintero, E. Up-regulation of gelatinases in the colorectal adenoma-carcinoma sequence. Eur. J. Cancer 2006, 42, 3246–3252.
[107]  Murname, M.J.; Cai, J.; Shuja, S.; McAneny, D.; Willett, J.B. Active matrix metalloproteinase-2 activity discriminates colonic mucosa, adenomas with and without high-grade dysplasia and cancers. Hum. Pathol 2011, 42, 688–701.
[108]  Decock, J.; Paridaens, R.; Ye, S. Genetic polymorphisms of matrix metalloproteinases in lung, breast and colorectal cancer. Clin. Genet 2008, 73, 197–211.
[109]  Langers, A.M.; Verspaget, H.W.; Hommes, D.W.; Sier, C.F. Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer. World J. Gastrointest. Oncol 2011, 3, 79–98.
[110]  Woo, M.; Park, K.; Nam, J.; Kim, J.C. Clinical implications of matrix metalloproteinase-1, -3, -7, -9, -12, and plasminogen activator inhibitor-1 gene polymorphisms in colorectal cancer. J. Gastroenterol. Hepatol 2007, 22, 1064–1070.
[111]  Park, K.S.; Kim, S.J.; Kim, K.H.; Kim, J.C. Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer. J. Gastroenterol. Hepatol 2011, 26, 391–397.
[112]  Xing, L.L.; Wang, Z.N.; Jiang, L.; Zhang, Y.; Xu, Y.Y.; Li, J.; Luo, Y.; Zhang, X. Matrix metalloproteinase-9-1562C > T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer. World J. Gastroenterol 2007, 13, 4626–4629.
[113]  Elander, N.; S?derkvist, P.; Fransén, K. Matrix metalloproteinase (MMP)-1, -2, -3 and -9 promoter polymorphsis in colorectal cancer. Anticancer Res 2006, 26, 791–795.
[114]  Xu, E.; Xia, X.; Lü, B.; Xinx, X.; Huang, Q.; Ma, Y.; Wang, W.; Lai, M. Association of matrix metalloproteinase-2 and -9 promoter polymorphisms with colorectal cancer in Chinese. Mol. Carcinog 2007, 46, 924–929.
[115]  Langers, A.M.; Sier, C.F.; Hawinkels, L.J.; Kubben, F.J.; van Duijn, W.; van der Reijden, J.J.; Lamers, C.B.; Hommes, D.W.; Verspaget, H.W. MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not. Br. J. Cancer 2008, 98, 1820–1823.
[116]  McColgan, P.; Sharma, P. Polymorphisms of matrix metalloproteinases 1, 2, 3 and 9 and susceptibility to lung, breast and colorectal cancer in over 30,000 subjects. Int. J. Cancer 2009, 125, 1473–1478.
[117]  Peng, B.; Cao, L.; Wang, W.; Xian, L.; Jiang, D.; Zhao, J.; Zhang, Z.; Wang, X.; Yu, L. Polymorphisms in the promoter regions of matrix metalloproteinases 1 and 3 and cancer risk: A meta-analysis of 50 case-control studies. Mutagenesis 2010, 25, 41–48.
[118]  Mroczko, B.; Groblewska, M.; Okulczyk, B.; Kedra, B.; Szmitkowski, M. The diagnostic value of matrix matalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) determination in the sera of colorectal adenoma and cancer patients. Int. J. Colorectal. Dis 2010, 25, 1177–1184.
[119]  Dragutinovic, V.V.; Radonjic, N.V.; Petrijevic, N.D.; Tatic, S.B.; Dimitrijevic, I.B.; Radovanovic, N.S.; Krivokapic, Z.V. Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer. Mol. Cell Biochem 2011, 355, 173–178.
[120]  Emara, M.; Cheung, P.Y.; Grabowski, K.; Sawicki, G.; Wozniak, M. Serum levels of matrix metalloproteinase-2 and -9 and conventional tumor markers (CEA and CA 19-9) in patients with colorectal and gastric cancer. Clin. Chem. Lab Med 2009, 47, 993–1000.
[121]  Wilson, S.; Damery, S.; Stocken, D.D.; Dowswell, G.; Holder, R.; Ward, S.T.; Redman, V.; Wakelam, M.J.; James, J; Hobbs, F.D.; et al. Serum matrix metalloproteinase 9 and colorectal neoplasia: A community-based evaluation of a potential diagnostic test. Br. J. Cancer 2012, 106, 1431–1438.
[122]  Nielsen, H.J.; Brünner, N.; Jorgensen, L.N.; Olsen, J.; Rahr, H.B.; Thygesen, K.; Hoyer, U.; Lauberg, S.; Stieber, P.; Blankenstein, M.A.; et al. Plasma TIMP-1 and CEA in detection of primary colorectal cancer: A prospective, population based study of 4509 high-risk individuals. Scand. J. Gastroenterol 2011, 46, 60–69.
[123]  Hurst, N.G.; Stocken, D.D.; Wilson, S.; Keh, C.; Wakelam, M.J.; Ismail, T. Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients. Br. J. Cancer 2007, 97, 971–977.
[124]  Wilson, S.; Raskila, T.; Ismail, T.; Stocken, D.D.; Martin, A.; Redman, V.; Wakelam, M.; Perry, I.; Hobbs, R. Establishing the added benefit of measuring MMP-9 in FOB positive patients as a part of the Wolverhampton colorectal cancer screening programme. BMC Cancer 2009, 9, 36.
[125]  Hritz, I.; Varga, M.Z.; Juhász, M.; Miheller, P.; Tulassay, Z.; Herszényi, L. Increased serum MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 levels in colorectal cancer development. Gastroenterology 2011, 140, S-343.
[126]  Nielsen, H.J.; Christensen, I.J.; Brünner, N. A novel prognostic index in colorectal cancer defined by serum carcinoembryonic antigen and plasma tissue inhibitor of metalloproteinases-1. Scand. J. Gastroenterol 2010, 45, 200–207.
[127]  Birgisson, H.; Nielsen, H.J.; Christensen, I.J.; Glimelius, B.; Brünner, N. Preoperative TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer: A prospective validation study. Eur. J. Cancer 2010, 46, 3323–3331.
[128]  Min, B.S.; Kim, N.K.; Jeong, H.C.; Chung, H.C. High levels of serum VEGF and TIMP-1 are correlated with colon cancer liver metastasis and intrahepatic recurrence after liver resection. Oncol. Lett 2012, 4, 123–130.
[129]  Pasternak, B.; Matthiessen, P.; Jansson, K.; Andersson, M.; Aspenberg, P. Elevated intraperitoneal matrix meetalloproteinases-8 and -9 in patients who develop anastomotic leakage after rectal cancer surgery: A pilot study. Colorectal Dis 2010, 12, e93–e98.
[130]  Jung, K.; Klotzek, S.; Stephan, C.; Mannello, F.; Lein, M. IMpact of blood sampling on the circulating matrix metalloproteinases 1, 2, 3, 7, 8, and 9. Clin. Chem 2008, 54, 772–773.
[131]  Jung, K. Is serum matrix metalloproteinase 9 a useful biomarker in detection of colorectal cancer? Considering pre-analytical interference that may influence diagnostic accuracy. Br. J. Cancer 2008, 99, 553–554.
[132]  Makowski, G.S.; Rambsy, M.L. Use of citrate to minimize neutrophil matrix metalloproteinase-9 in human plasma. Anal. Biochem 2003, 322, 283–286.
[133]  Wu, C.Y.; Wu, M.S.; Chiang, E.P.; Chen, C.J.; Chi, N.H.; Shih, Y.T.; Chen, G.H.; Lin, J.T. Plasma matrix metalloproteinase-9 level to predict gastric cancer evolution. Clin. Cancer Res 2007, 13, 2054–2060.
[134]  Gerlach, R.F.; Meschiari, C.A.; Marcaccini, A.M.; Palei, A.C.; Sandrim, V.C.; Cavalli, R.C.; Tanus-Santos, J.E. Positive correlations between serum and plasma matrix metalloproteinase (MMP)-2 and MMP-9 levels in disease conditions. Clin. Chem. Lab Med 2009, 47, 888–891.
[135]  Gerlach, R.F.; Demacq, C.; Jung, K.; Tanus-Santos, J.E. Rapid separation of serum does not avoid artificially higher matrix metalloproteinase (MMP)-9 levels in serum versus plasma. Clin. Biochem 2007, 40, 119–123.
[136]  S?rensen, N.M.; Bystr?m, P.; Christensen, I.J.; Berglund, A.; Nielsen, H.J.; Brünner, N.; Glimelius, B. TIMP-1 is significantly associated with objective response and survival in metastatic colorectal cancer patients receiving combination of irinotecan, 5-fluorouracil, and folinic acid. Clin. Cancer Res 2007, 13, 4117–4122.
[137]  Bourboulia, D.; Jensen-Taubman, S.; Rittler, M.R.; Han, H.Y.; Chatterjee, T.; Wei, B.; Stetler-Stevenson, W.G. Endogenous angiogenesis inhibitor blocks tumor growth via direct and indirect effects on tumor microenvironment. Am. J. Pathol 2011, 179, 2589–2600.
[138]  Boudreau, N.; Sympson, C.J.; Werb, Z.; Bissel, M.J. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science 1995, 267, 891–893.
[139]  Murphy, F.R.; Issa, R.; Zhou, X.; Ratnarajah, S.; Nagase, H.; Arthur, M.J.; Benyon, C.; Iredale, J.P. Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibitor: Implications for reversibility of liver fibrosis. J. Biol. Chem 2002, 277, 11069–11076.
[140]  Alduaymi, B.; Christensen, I.J.; S?létormos, G.; Jess, P.; Nielsen, S.E.; Brünner, N.; Nielsen, H.J. Changes in soluble CEA and TIMP-1 levels during adjuvant chemotherapy for stage III colon cancer. Anticancer Res 2010, 30, 233–237.
[141]  Bozec, L.; Bierling, P.; Fromont, P.; Lévi, F.; Debat, P.; Cvitkovic, E.; Misset, J.L. Irinotecan-induced immune thrombocytopenia. Ann. Oncol 1998, 9, 453–455.
[142]  S?rbye, H.; Bruserud, Y.; Dahl, O. Oxaliplatin-induced haematological emergency with an immediate severe thrombocytopaenia and haemolysis. Acta Oncol 2001, 40, 882–883.
[143]  Curtis, B.R.; Kaliszewszki, J.; Marques, M.B.; Saif, M.W.; Nabelle, L.; Blank, J.; McFarland, J.G.; Aster, R.H. Immune-mediated thrombocytopaenia resulting from sensitivity to oxaliplatin. Am. J. Hematol 2006, 81, 193–198.
[144]  Bautista, M.A.; Stevens, W.T.; Chen, C.S.; Curtis, B.R.; Aster, R.H.; Hsueh, C.T. Hypersensitivity reaction and acute immune-mediated thrombocytopaenia from oxaliplatin: Two case reports and a review of the literature. J. Hematol. Oncol 2010, 3, 12.
[145]  Ramer, R.; Eichele, K.; Hinz, B. Upregulation of tissue inhibitor matrix metalloproteionases-1 confers the anti-invasive action of cisplatin on human cancer cells. Oncogenes 2007, 26, 5822–5827.
[146]  Ramer, R.; Hinz, B. Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinase-1. J. Natl. Cancer Inst 2008, 100, 59–69.
[147]  Cattaneo, M.; Fontanella, E.; Canton, C.; Delia, D.; Biunno, I. SEL1L affects human pancreatic cancer cell cycle and invasiveness through modulation of PTEN and genes related to cell-matrix interactions. Neoplasia 2005, 7, 1030–1038.
[148]  Park, H.J.; Lee, H.J.; Min, H.Y.; Chung, H.J.; Suh, M.E.; Park-Choo, H.Y.; Kim, C.; Kim, H.J.; Seo, E.K.; Lee, S.K. Inhibitory effect of a benz(f)indole-4,9-dione analog on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells. Eur. J. Pharmacol 2005, 527, 31–36.
[149]  Park, M.J.; Lee, H.J.; Park, C.M.; Lee, H.C.; Woo, S.H.; Jin, H.O.; Han, C.J.; An, S.; Lee, S.H.; Chung, H.Y.; et al. Arsenic trioxide (As2O3) inhibits invasion of HT1080 human fibrosarcoma cells: Role of nuclear factor-κ,B and reactive oxygen species. J. Cell Biochem 2005, 95, 955–969.
[150]  Watanabe, T.; Kobunai, T.; Yamamoto, Y.; Matsuda, K.; Ishihara, S.; Nozawa, K.; Iinuma, H.; Ikeuchi, H. Gene expression of vascular endothelial growth factor A, thymidylate synthase, and tissue inhibitor of metalloproteinase 3 in prediction of response to bevacizumab treatment in colorectal cancer. Dis. Colon. Rectum 2011, 54, 1026–1035.
[151]  Manello, F.; Tonti, G.; Pap, S. Matrix metalloproteinase inhibitors as targets of anticancer therapeutics. Curr. Cancer Drugs Targets 2005, 5, 285–298.
[152]  Manello, F. Natural bio-drugs as matrix metalloproteinase inhibitors: New perspectives on the horizon? Recent Pat. Anticancer Drug Discover 2006, 1, 91–103.
[153]  Gialeli, C.; Theocharis, A.D.; Karamanos, N.K. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 2011, 278, 16–27.
[154]  Tu, G.; Xu, W.; Huang, H.; Li, S. Progress in the development of matrix metalloproteinase inhibitors. Curr. Med. Chem 2008, 15, 1388–1395.
[155]  Zucker, S.; Cao, J.; Chen, W.T. Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 2000, 19, 6642–6650.
[156]  Li, X.; Wu, J.F. Recent developments in patent anti-cancer agents targeting the matrix metalloproteinases (MMPs). Recent Pat. Anticancer Drug Discov 2010, 5, 109–141.
[157]  López-Otín, C.; Matrisian, L.M. Emerging roles of proteases in tumour suppression. Nat. Rev. Cancer 2007, 7, 800–809.
[158]  Zucker, S.; Cao, J. Selective matrix metalloproteinase (MMP) inhibitors in cancer therapy: Ready for prime time? Cancer Biol. Ther 2009, 8, 2371–2373.
[159]  Dormán, G.; Cseh, S.; Hajdú, I.; Barna, L.; Kónya, D.; Kupai, K.; Kovács, L.; Ferdinandy, P. Matric metalloproteinase inhibitors: A critical appraisal of design principles and proposed therapeutic utility. Drugs 2010, 70, 949–964.
[160]  Fingleton, B. MMPs as therapeutic targets-still a viable option? Semin. Cell Dev. Biol 2008, 19, 61–68.
[161]  Peterson, J.T. The importance of estimating the therapeutic index in the development of matrix metalloproteinase inhibitors. Cardiovasc. Res 2006, 698, 677–687.
[162]  King, J.; Zhao, J.; Clingan, P.; Morris, D. Randomised double blind placebo control study of adjuvant treatment with the metalloproteinase inhibitor, Marimastat in patients with inoperable colorectal hepatic metastases: Significant survival advantage in patients with musculoskeletal side-effects. Anticancer Res 2003, 23, 639–645.
[163]  Swarnakar, S.; Paul, S.; Singh, L.P.; Reiter, R.J. Matrix metalloproteinases in health and disease: Regulation by melatonin. J. Pineal. Res 2011, 50, 8–20.
[164]  Hadler-Olsen, E.; Fadnes, B.; Sylte, I.; UhlinHansen, L.; Winberg, J.O. Regulation of matrix metalloproteinase activity in health and disease. FEBS J 2011, 278, 28–45.
[165]  Bauvois, B. New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: Outside-in signaling and relationship to tumor progression. Biochim. Biophys. Acta 2012, 1825, 29–36.
[166]  Overall, C.M.; Kleifield, O. Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat. Rev. Cancer 2006, 6, 226–239.
[167]  Sela-Passwell, N.; Rosenblum, G.; Shohan, T.; Sagi, I. Structural and functional bases for allosteric control of MMP activities: Can it pave the path for selective inhibition? Biochim. Biophys. Acta 2010, 1803, 29–38.
[168]  Kapral, M.; Wawszczyk, J.; Jurzak, M.; Hollek, A.; Weglarz, L. The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells. Int. J. Colorectal Dis 2012, doi:10.1007/s00384-012-1445-3.
[169]  Wang, J.; Ding, W.; Sun, B.; Jing, R.; Huang, H.; Shi, G.; Wang, H. Targeting of colorectal cancer growth, metastasis, and anti-apoptosis in BALB/c nude mice via APRIL siRNA. Mol. Cell Biochem 2012, 363, 1–10.
[170]  Hsu, H.H.; Liu, C.J.; Shen, C.Y.; Chen, Y.J.; Chen, L.M.; Kuo, W.H.; Lin, Y.M.; Chen, R.J.; Tsai, C.H.; Tsai, F.J.; et al. p38α MAPK mediates 17β-estradiol inhibition of MMP-2 and -9 expression and cell migration in human lovo colon cancer cells. J. Cell Physiol 2012, 227, 3648–3660.
[171]  Saitou, T.; Itano, K.; Hoshino, D.; Koshikawa, N.; Seiki, M.; Ichikawa, K.; Suzuki, T. Control and inhibition analysis of complex formation processes. Theor. Biol. Model 2012, 9, 33.
[172]  Konstantinopoulos, P.A.; Karamouzis, M.V.; Papatsoris, A.G.; Papavassiliou, A.G. Matrix metalloproteinase inhibitors as anticancer agents. Int. J. Biochem. Cell Biol 2008, 40, 1156–1168.

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