Matrix metalloproteinases (MMPs) in cancer initiation and progression

Abstract

Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containingpeptidehydrolase, which are actively involved in degradation of the extracellularmatrix (ECM), organ development, and tissue remodeling to maintain homeostasisof tissue. Through degradation of ECM in tumor, MMPs providefundamental base for further tumor cell metastasis. The complex constitution oftumor microenvironment permits various types of regulatory mechanism andexpression of cascades of MMPs. Through which various functions of MMPs canbe determined. The physiological role of MMP enzymes can be determined bytheir location and time frame of its activity during tumor progression. Accordingto the recent studies which have revealed the diverse functions of MMPs otherthan ECM degradation, MMPs are known to play a major role in regulation ofmany signaling pathways. Their participation in such pathways helps in alteringcell physiology as well as in combating disease. MMPs regulate initiation ofapoptosis in tumor cells through cleavage of ligands or receptors. There areevidences which support MMPs role in angiogenic and lymph-angiogenicprocesses. Most of the studies suggest the major involvement of MMP-2, MMP-9, and MMP-14 in tumor angiogenesis, and to a smaller extent, MMP-1and MMP-7 are also known to be involved. MMPs also play a prominent role ingeneration of growth signals, apoptosis regulation, tumor vasculature, initiationof neoplastic progression, invasion and metastasis, metastatic niche formation, and MMPs orchestrate inflammation in cancer. Some other non-proteolytic functions of MMPs are also important to be considered in cancer. Wide range of MMPs role in cancer initiation and progression also provides wide range of therapeutic opportunity for cancer treatment.