Effect of hypoxia on human seminoma cells

Int J Oncol. 2002 May;20(5):955-62.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Adhesion
  • Cell Cycle Proteins / metabolism
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27
  • DNA, Complementary / metabolism
  • Endothelial Growth Factors / biosynthesis
  • Flow Cytometry
  • G1 Phase
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Hypoxia*
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Lymphatic Metastasis
  • Male
  • RNA / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Seminoma / metabolism*
  • Seminoma / pathology
  • Testicular Neoplasms / metabolism*
  • Testicular Neoplasms / pathology
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / metabolism
  • Up-Regulation*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C

Substances

  • CDKN2B protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Complementary
  • Endothelial Growth Factors
  • HSP70 Heat-Shock Proteins
  • Hyaluronan Receptors
  • Tumor Suppressor Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Intercellular Adhesion Molecule-1
  • Cyclin-Dependent Kinase Inhibitor p27
  • RNA