Participation of Stromal component in Cancer Progression

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The invasion and metastasis of cancer cells has been proposed to be mediated by the surrounding microenvironment such as stromal cells and extracellular matrix proteins. We have demonstrated that fibroblasts secrete a chemotactic factor and enhance the motility of oral cancer cells. Tumor invasion and metastasis are also mediated by proteolytic enzymes that degrade extracellular matrix proteins. Matrix metalloproteinase-2 (MMP-2) degrades the major components of basement membrane such as type IV collagen, laminin and fibronectin. In various tumors including squamous cell carcinoma (SCC), increased production of MMP-2 has been associated their invasive and metastatic potential. However, MMPs including MMP-2, MMP-9 and stromelysin are not systematically secreted by tumor cells themselves but by nonmalignant stromal cells in the peritumoral host tissues.To assess the participation of stromal components in the proteolytic activity of SCC cells, we investigated the effect of fibroblasts on MMP-2 activation on the surface of SCC cells. SCC cells examined in this study serereted no MMP-2 and the plasma membrane of SCC cells failed to bind MMP-2 and activate it. However, treatment of SCC cells with fibroblast-conditioned medium (fibroblast-CM) led to the enhancement of MMP-2 binding and activation on the cell surface. Moreover, fibroblasts induced the expression of membrane type 1 MMP (MT1-MMP) in SCC cells. These findings suggest that fibroblasts might facilitate the invasion of SCC cells by increasing the proteolytic activity on the surfaces of SCC cells.