RECENT DATA ON METALLOPROTEINASES, OBLIGA TORY PARTNERS OF TUMOR PROGRESSION

Metastasis is a complex process that requires sequential interactions between the invasive cell and the extracellular matrix. These interact ions are characterized by cell adhesion and migration. Cell adhesion i nvolves specific receptors. Migration requires the induction and secre tion 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 re ach the extracellular matrix, the MMPs undergo an activation step whic h involves plasmin, growth factors or membrane-type matrix metalloprot einases (MT-MMPs). The molecular mechanisms involves protein-kinase C activation. MMPs are associated with tissue inhibitors of metalloprote inases (TIMPs) with which they form high affinity non covalent 1:1 com plexes. Upregulation of MMPs or down regulation of TIMPs lead to an im balance of this ratio which favours invasive process. Consequently, th e development of matrix metalloproteinase inhibitors such as Batimasta t may provide interesting tools for cancer therapy.