Effect of hypoxia on human seminoma cells.

Since hypoxia has been considered to enhance metastatic potential in solid tumors via a neo-angiogenesis caused by vascular endothelial cell growth factors (VEGFs) induced by hypoxia inducible factor-1alpha (HIF-1alpha), the effects of hypoxia on human seminoma cell lines were examined in terms of growth, morphology, gene expression, protein expression and cell cycle perturbation. Growth was inhibited in long-term cultures with morphological changes to the spindle form. The gene expression of VEGF-C was markedly enhanced and the production of VEGF-A increased during hypoxia, although HIF-1alpha was not upregulated at the protein or message level. Hypoxic culture caused G1 cell cycle arrest with upregulation of the p15/ink4b and p27/Kip1 genes, whereas no increase of apoptotic cells was observed on up-regulation of the heat shock protein (HSP) 70 gene. The adhesion molecules were only slightly altered.