Impact of vascular endothelial growth factor release on radiation resistance

Juergen Brieger1, Jana Kattwinkel, Manfred Berres

  • 1Department of Otorhinolaryngology, Head and Neck Surgery, Molecular Tumor Biology Laboratory, University Hospital of Mainz, 55101 Mainz, Germany. brieger@mail.uni-mainz.de

Oncology Reports
|November 6, 2007
PubMed

Insights

Irradiated tumors release vascular endothelial growth factor (VEGF), enhancing tumor cell survival and radiation resistance. Higher VEGF release after irradiation strongly correlates with increased resistance in various cancer cell lines.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiation Oncology

Background:

  • Irradiation can induce an angiogenic response in tumors, potentially decreasing their sensitivity to radiation.
  • The specific contribution of growth factors like vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) released post-irradiation to tumor resistance is not well understood.

Purpose of the Study:

  • To investigate the release of VEGF and bFGF by different cancer cell lines following irradiation.
  • To correlate the levels of released VEGF and bFGF with the cells' resistance to irradiation.
  • To explore the potential autocrine mechanisms involving VEGF and its receptors in radiation resistance.

Main Methods:

  • In vitro analysis of VEGF and bFGF release from six epithelial tumor cell lines (HNSCC, RCC, OC) before and after irradiation (2 or 6 Gy).
  • Quantification of released growth factors using ELISA assays.
  • Assessment of cell survival rates via colony assays to determine radiation resistance.
  • Immunohistochemical analysis of VEGF and its receptors (FLK, FLT, NRP1) expression.

Main Results:

  • VEGF release significantly increased in all tested cell lines post-irradiation (p<0.05), with the highest increase observed in renal cell carcinoma (RCC) lines.
  • Radiation resistance showed a strong positive correlation with both the absolute level and the relative increase of VEGF release after irradiation (r>0.9, p<0.01).
  • Basic fibroblast growth factor (bFGF) levels did not correlate with radiation resistance.

Conclusions:

  • Tumor cell survival after irradiation may be promoted by released VEGF, suggesting an autocrine protective mechanism.
  • The level of VEGF released by tumor cells post-irradiation is a direct indicator of their resistance to radiation treatment.
  • Targeting VEGF-mediated pathways could be a strategy to overcome radiation resistance in certain cancers.

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