ESTABLISHMENT OF ANTI-LYMPHANGIOGENETIC THERAPY BY CANCER SPECIFIC s-VEGFR-3.

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Expression of VEGF family in OSCC cell lines.To examine the expression profile of VEGF family on squamous cell carcinoma cell lines NA and HSC-4, we performed RT-PCR analysis. As results, both cells expressed VEGF-C and VEGF-D. The expression of VEGFR was not detected in both cells.Involvement of HGF-Met system in the invasiveness of OSCC cells.It is well known that the expression of VEGF is highly regulated by c-Met, a counter part of hepatocyto growth factor (HGF). Thus, we examined the expressions of c-Met and HGF by RT-PCR in both OSCC cells. Although HGF was not expressed in OSCC cells, c-Met was highly expressed in both cells.The cancer cells survive in the situation of low oxygen called HYPOXIA in tumor mass. The cells under hypoxia express HIF, a nuclear factor and acquire the survival potential. HIF exist in upstream of c-Met,MMPs,VEGF and influence the invasiveness of cancer cells. Therefore, we performed RT-PCR for HIF on OSCC cells in hypoxia chamber. Both cells expressed HIF-1 in hypoxia and c-Met is also induced. Interestingly, invasion assay in hypoxia chamber revealed highly invasiveness of OSCC cells. To examine the mechanism of this up-regulation of invasiveness, we performed RT-PCR, western blotting and ELISA for MMP-2, a major matrix metalloproteinase for resolution of basement membrane in human. As results, the cells cultured in hypoxia chamber expressed high concentration of MMP-2 in the culture supernatant.