Matrix Metalloproteases

Matrix metalloproteases (matrix metalloproteinase, MMPs), also called matrixins, are zinc-dependent endopeptidases that are the major proteases involved in ECM degradation. MMPs are capable of degrading a wide range of extracellular molecules and a number of bioactive molecules.

24 matrixin genes have been identified in humans, which can be organized into six groups based on domain organization and substrate preference:

1. Collagenases (MMP-1, -8 and -13)
2. Gelatinases (MMP-2 and MMP-9)
3. Stromelysins (MMP-3, -10 and -11)
4. Matrilysin (MMP-7 and MMP-26)
5. Membrane-type (MT)-MMPs (MMP-14, -15, -16, -17, -24 and -25)
6. Other (MMP-12, -19, -20, -21, -23, -27 and -28)

Following stepwise activation by proteinases, MMP activity is regulated by two major endogenous inhibitors: α2-macroglobulin and tissue inhibitors of metalloproteases (TIMPs 1-4).

MMPs play a central role in cell proliferation, migration, differentiation, angiogenesis, apoptosis and host defences. Dysregulation of MMPs has been implicated in many diseases including arthritis, chronic ulcers, encephalomyelitis and cancer. Tumor metastasis is a multistep process involving the dissemination of tumor cells from the primary tumor to secondaries at a distant organ or tissue. One of the first steps in metastasis is the degradation of the basement membrane, a process in which MMPs have been implicated. MMPs are secreted by tumor cells themselves or by surrounding stromal cells stimulated by the nearby tumor. Numerous studies have linked altered MMP expression in different human cancers with poor disease prognosis. MMP-1, -2, -3, -7, -9, -13 and -14 all have elevated expression in primary tumors and/or metastases. Synthetic or natural inhibitors of MMPs result in inhibition of metastasis, while up-regulation of MMPs led to enhanced cancer cell invasion.

External sources of pharmacological information for Matrix Metalloproteases :

• BJP Guide

Literature for Matrix Metalloproteases

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Angiogenesis in Cancer Poster

This poster summarizes the pathogenesis of angiogenesis in cancer, as well as some of the main angiogenesis therapeutic targets.

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Matrix Metalloprotease (MMP) Gene Data