Effects of hypoxia on human seminoma cell lines *
Hypoxia is considered to play an important role in tumor progression through vascular endothelial growth factors (VEGF). In this study, the effects of hypoxia on human testicular seminoma cells were analyzed. A human testicular seminoma line (JKT-1) and its highly metastatic subline (JKT-HM), established at Kawasaki Medical School, were used to analyze the effects of hypoxia on these cells with regard to growth, morphological changes, production of VEGF-A, and various gene expressions including angiogenic factors, induction of apoptosis, and cell cycle perturbation. Hypoxia suppressed cell growth, caused morphological changes that transformed the cells into large and spindle-shaped cells, and enhanced VEGF-A production in both lines. In JKT-1 cells, the gene expressions of VEGF-A, -B, and -D were enhanced until day 2 in hypoxia, and then reduced. However, VEGF-C expression was enhanced continuously. There was no change in HIF-1 (hypoxia inducible factor-l) gene expression. In addition, upregulation of stress proteins (HSP70 and HSP90), cyclin-dependent kinase-inhibitors (CDK-Is) (p21, p27, and pl5), and adhesion molecules (CD44 and Vimentin) was observed in JKT-1 cells cultured in hypoxia. Although both lines showed G1 cell cycle block in hypoxia, no appearance of apoptotic fractions was noted. These results indicate that the upregulation of angiogenic factors caused by hypoxia was observed in seminoma cells in similar manner to that in other solid tumors. Specifically, the constitutive upregulation of VEGF-C, which has been identified as one of the most important factors in lymphatic metastasis of cancer cells as well as VEGF-D, lead us to clariby the role of this factor in clinical lymphatic metastasis found in seminoma patient in the future. (Accepted on December 20, 2001) Kawasaki Igakkaishi 28(1) : 23 ―31, 2002
