Matrix Metalloproteinases (MMPs) in Cancer Initiation and Progression

Abstract

Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing peptidehydrolase, which are actively involved in degradation of the extracellular matrix (ECM), organ development, and tissue remodeling to maintain homeostasis of tissue. Through degradation of ECM in tumor, MMPs provide fundamental base for further tumor cell metastasis. The complex constitution of tumor microenvironment permits various types of regulatory mechanism and expression of cascades of MMPs. Through which various functions of MMPs can be determined. The physiological role of MMP enzymes can be determined by their location and time frame of its activity during tumor progression. According to the recent studies which have revealed the diverse functions of MMPs other than ECM degradation, MMPs are known to play a major role in regulation of many signaling pathways. Their participation in such pathways helps in altering cell physiology as well as in combating disease. MMPs regulate initiation of apoptosis in tumor cells through cleavage of ligands or receptors. There are evidences which support MMPs role in angiogenic and lymph-angiogenic processes. 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-1 and MMP-7 are also known to be involved. MMPs also play a prominent role in generation of growth signals, apoptosis regulation, tumor vasculature, initiation of 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.