Molecular and clinical insights of matrix metalloproteinases into cancer spread and potential therapeutic interventions

Abstract

Matrix metalloproteinases (MMPs) are the group of enzymes that belong to the family of zinc dependent endopeptidases. These proteases degrade collagen and other important proteins in extracellular matrix (ECM) and regulate cytoskeletal proteins, growth factors, chemokines and cytokines, thereby play significant role during organogenesis and normal tissue turnover. Recent studies highlight the tumorigenic functions of MMPs by modulating tumor microenvironment. Dysregulated MMPs/TIMPs cause an imbalance in crucial cell signals, and lead to serious pathological conditions related to inflammation, uncontrolled cell growth, ECM degradation, increased cell migration, cell death resistance, replicative immortality and the establishment of metastatic niche at secondary sites. Recently established correlation between the higher expression of active MMPs and cancer aggressiveness makes them probable target candidate of cancer diagnosis, prognosis and therapy. The present review focuses on the tumourigenic functions of MMPs and recent advancements in the development of MMP inhibitors of therapeutic potential in cancer treatment.

Keywords: Cancer therapy; Extracellular matrix; Matrix metalloproteinases; Matrix metalloproteinases inhibitors; Tumor microenvironment; Tumorigenesis.