[The metalloproteinases in cancer].
Tumor growth and metastatic dissemination are associated to important tissue remodelling involving matrix metalloproteinases (MMPS) acting in a concerted manner with serine proteases. Initially, it was generally accepted that proteases produced by tumor cells promote their invasive capacities by degrading extracellular matrix components. On the opposite, protease inhibitors were viewed as anti-cancer molecules. Recently, new insights into the understanding of peritumoral proteolysis were given by complete human genome sequencing and by improvement in transgenesis leading to the generation of mice deficient for genes of different proteolytic systems. Our work has evidenced the production of proteases and their inhibitors by host cells rather than by tumor cells themselves. It demonstrates the multifunctionality of proteases which can exert different effects by controlling several steps of cancer progression such as tumor growth, angiogenesis and invasion. It identifies these cells, whose genome is more stable than that of cancer cells, as potential therapeutic targets.
Noël
A
A
Laboratoire de Biologie des Tumeurs et du Développement Centre de Recherche en Cancérologie expérimentale.
Foidart
J-M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D045726:Metalloproteases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011480:Protease Inhibitors / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D045726:Metalloproteases