[Current data on metalloproteinases, obligatory partners of tumor progression]

Abstract

Metastasis is a complex process that requires sequential interactions between the invasive cell and the extracellular matrix. These interactions are characterized by cell adhesion and migration. Cell adhesion involves specific receptors. Migration requires the induction and secretion of proteolytic enzymes belonging to the matrix metalloproteinases (MMP) family. In most cancers, stromal cells secrete collagenases or gelatinases under the influence of cancer cells. The MMPs are secreted as inactive forms. In order to cross basement membrane and then to reach the extracellular matrix, the MMPs undergo an activation step which involves plasmin, growth factors or membrane-type matrix metalloproteinases (MT-MMPs). The molecular mechanisms involves protein-kinase C activation. MMPs are associated with tissue inhibitors of metalloproteinases (TIMPs) with which they form high affinity non covalent 1:1 complexes. Upregulation of MMPs or down regulation of TIMPs lead to an imbalance of this ratio which favours invasive process. Consequently, the development of matrix metalloproteinase inhibitors such as Batimastat may provide interesting tools for cancer therapy.