Regulation of the expression of pigment epithelium-derived factor, an anti-angiogenic factor in human oral squamous cell carcinoma cell lines

Angiogenesis plays an important role in tumor growth and metastasis and is regulated by a balance between angiogenic stimulators and inhibitors. We investigated the gene expression profile of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic factor, in human oral squamous cell carcinoma (SCC) cell lines. The treatment of SCC cells with hypoxia increased the expression of PEDF as well as VEGF. Moreover, the treatment of SCC cells with VEGF enhanced the expression of PEDF mRNA and secretion of PEDF. In LMF-4, a SCC clone producing abundant VEGF and PEDF, the addition of neutralizing VEGF antibody substantially blocked PEDF expression. These data suggest that human oral squamous cell carcinoma cells produce VEGF, which in turn regulates PEDF production, and this balance may be contributing to neovascularization in tumors.