Les protéases stromales dans la progression cancéreuse mammaire

Matrix metalloproteases represent a family of proteases secreted as latent inactive enzymes able to degrade the majority of extracellular matrix components. These enzymes are overexpressed during several pathological tissue remodelings including tumor progression and tumor invasion. It was indeed classically admitted that matrix metalloproteases involved in tumoral progression were preferentially expressed by cancerous cells. Our studies on gelatinase A and stromelysin-3 have, however, demonstrated that their messenger RNAS are detected in fibroblasts of the peritumoral stroma in human mammary carcinoma and not in the cancerous cells themselves. By immunohistochemistry, we have detected gelatinase A in the cytoplasm of fibroblasts and at the surface of the tumor cells. This membrane localization of the protein could result from its binding, following secretion by the neighbouring stromal cells, to a specific binding site expressed at the surface of the carcinoma cells. These cells are indeed able to induce an increased proteolytic activity by enhancing the transcription of these enzymes by peritumoral fibroblasts. These enzymes represent therefore potential targets for the development of new therapeutic strategies.