MAMMARY-TUMOR INVASION - THE KEY ROLE OF NORMAL-CELLS IN HOST TISSUES

Tumor progression is influenced by extracellular matrices and by solub le factors or cytokines locally produced by host tissue cells (fibrobl asts, immune cells ...). Such factors may also accumulate in close ass ociation with some extracellular matrix molecules in the tumor. They m ay also be unmasked during breaking down of extracellular matrices [11 -16, 38, 39]. The most insidious aspect of tumors is their propensity to locally invade normal tissues of the host and to form secondary foc i in organs at distant sites from the primary tumor called metastases. During this process, invasive cells come into contact with host tissu e cells such as fibroblasts, endothelial cells, macrophages, lymphocyt es ... These cells are not the passive witnesses of the metastatic cas cade but actively participate to the malignant invasion. Through solub le messages (cytokines) and through insoluble molecules of the extrace llular matrix, neoplastic and normal cells mutually modulate their act ivities. Cancer cells regulate the biosynthetic activities of fibrobla sts and alter in this way the scaffold of the tumor [7, 16-19, 36]. Re ciprocally, host cells secrete extracellular matrix proteins and cytok ines which influence the growth and activities of tumor cells [1-7, 12 -15, 34, 35, 39]. They also produce at the periphery of tumor cells pr oteolytic enzymes which promote host tissue destruction and cancerous cells migration [11, 20, 21]. Among these enzymes, matrix metalloprote inases appear to play a key role during invasion and metastasis [40, 4 1, 43-57]. Tumors represent thus a complex ecosystem. Tumor cells inte ract with several components of the extracellular matrix and with host cells (immune cells, fibroblasts, endothelial cells). Such multiple c ell-cell and cell-matrix interactions condition angiogenesis, tumor gr owth, destruction of host tissues, local migration of cancer cells and their metastatic dissemination. It is probable that a precise knowled ge of the genes which are selectively activated in tumors under.the in fluence of the host cells or of the tumor cells will allow to define n ew therapeutic strategies. These treatments will aim not at destroying the metastatic neoplastic cells but at preventing their growth by int erfering with their microenvironment.