matrix metalloproteinases in cancer progression

Abstract In the 1980’s, as the importance of matrix metalloproteinases (MMPs) in cancer progression was dis-covered, it was recognized that in most tumors these proteases were abundantly and sometimes exclusively expressed not by tumor cells, but by normal host-derived cells like fibrob-lasts, vascular endothelial cells, myofibroblasts, pericytes or inflammatory cells that contribute to the tumor microenviron-ment. Later experiments in mice deficient in specific MMPs revealed that host-derived MMPs play a critical role not only in tumor cell invasion, but also in carcinogenesis, angiogene-sis, vasculogenesis and metastasis. Tumor cells secrete many factors, cytokines and chemokines that directly or indirectly increase the expression of these MMPs in the tumor microen-vironment where they exert extracellular matrix (ECM) de-grading and sheddase activities. The knowledge of the com-plex role that stromal-derived MMPs play in the interaction between tumor cells and stromal cells should allow us to consider specific windows in cancer treatment when MMP inhibition could have a valuable therapeutic effect