Glioma cells suppress hypoxia-induced endothelial cell apoptosis and promote the angiogenic process

  • Authors:
    • Ravesanker Ezhilarasan
    • Indra Mohanam
    • Kathiravan Govindarajan
    • Sanjeeva Mohanam
  • View Affiliations

  • Published online on: March 1, 2007     https://doi.org/10.3892/ijo.30.3.701
  • Pages: 701-707
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Abstract

The hypoxic microenvironment of solid tumors is associated with malignant progression and it renders tumors more resistant to cancer therapies. Endothelial cell damage may occur following hypoxic conditions and lead to dysfunction; however, endothelial cells in tumors survive hypoxic conditions providing nutrients and oxygen to facilitate tumor growth. In this study, we investigated the effects of tumor-conditioned medium on hypoxia-induced changes in endothelial cell growth, migration and survival. Tumor conditioned medium collected from U87 human glioblastoma cells were applied to endothelial cultures in normoxia or hypoxia conditions. Hypoxia caused a reduction in clonogenic cell survival response and an increase of the sub-G1 phase of the cell cycle in endothelial cells. Cell migration was measured by spheroid and wound-induced migration assays and hypoxia compared with normoxia significantly increased the number of migrating endothelial cells. Nuclear staining with Hoechst 33258 and caspase-9 and -3 activation in endothelial cells show that hypoxia-induced apoptosis involves caspase-dependent mechanism. Exposure to hypoxia caused an increase in gene expression of VEGF and VEGFR2 and activities of MMP-2 and MMP-9. Furthermore, hypoxia induced an increase in capillary-like structure formation in endothelial cells seeded into Matrigel. Tumor conditioned medium enhanced survival and rescued endothelial cells from apoptosis induced by hypoxia. These molecular changes in endothelial cells could, in part, contribute to the angiogenic response that occurs during hypoxia-induced angiogenesis in glial tumors.

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March 2007
Volume 30 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ezhilarasan R, Mohanam I, Govindarajan K and Mohanam S: Glioma cells suppress hypoxia-induced endothelial cell apoptosis and promote the angiogenic process. Int J Oncol 30: 701-707, 2007.
APA
Ezhilarasan, R., Mohanam, I., Govindarajan, K., & Mohanam, S. (2007). Glioma cells suppress hypoxia-induced endothelial cell apoptosis and promote the angiogenic process. International Journal of Oncology, 30, 701-707. https://doi.org/10.3892/ijo.30.3.701
MLA
Ezhilarasan, R., Mohanam, I., Govindarajan, K., Mohanam, S."Glioma cells suppress hypoxia-induced endothelial cell apoptosis and promote the angiogenic process". International Journal of Oncology 30.3 (2007): 701-707.
Chicago
Ezhilarasan, R., Mohanam, I., Govindarajan, K., Mohanam, S."Glioma cells suppress hypoxia-induced endothelial cell apoptosis and promote the angiogenic process". International Journal of Oncology 30, no. 3 (2007): 701-707. https://doi.org/10.3892/ijo.30.3.701