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The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer
Second Department of Medicine, Semmelweis University, H-1088 Budapest, Szentkirályi str. 46, H-1088, Hungary
First Department of Medicine, Fejér County Szent György Hospital, Székesfehérvár, H-8000, Hungary
Department of Oncology, Szent László Hospital, Budapest, H-1097, Hungary
* Author to whom correspondence should be addressed.
Received: 28 August 2012; in revised form: 8 October 2012 / Accepted: 10 October 2012 / Published: 16 October 2012
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.
Keywords: matrix metalloproteinase; tissue inhibitor of matrix metalloproteinase; colorectal cancer; adenoma; tumor progression; invasion; metastasis; prognosis; biomarker
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Herszényi, L.; Hritz, I.; Lakatos, G.; Varga, M.Z.; Tulassay, Z. The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer. Int. J. Mol. Sci. 2012, 13, 13240-13263.
Herszényi L, Hritz I, Lakatos G, Varga MZ, Tulassay Z. The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer. International Journal of Molecular Sciences. 2012; 13(10):13240-13263.
Herszényi, László; Hritz, István; Lakatos, Gábor; Varga, Mária Z.; Tulassay, Zsolt. 2012. "The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer." Int. J. Mol. Sci. 13, no. 10: 13240-13263.