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Updated: Jul 10, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
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
Abstract:
There is increasing evidence of an angiogenic response of irradiated tumors resulting in decreased radiation sensitivity. However, little is known about the contribution of tumor vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF)-release induced by irradiation to the individual level of resistance. In this in vitro study, we analysed the VEGF- and bFGF-release of six epithelial tumor cell lines before and after irradiation and correlated these data to the corresponding irradiation resistance. Two head and neck squamous cell carcinoma (HNSCC), two renal cell carcinoma (RCC), and two ovarian cancer (OC) cell lines were each exposed to 2 or 6 Gy single dose using a 137Cs-source. Non-irradiated controls were processed in parallel. Survival rates were assessed by colony assays as a measure of resistance. The released VEGF and bFGF was quantified by ELISA assays. Additionally, the expression of VEGF and its respective receptors (FLK, FLT, and NRP1) was visualized by immunohistochemistry. VEGF-release was significantly increased (p<0.05) in all cell lines after irradiation. Release was most prominent in the RCC cell lines, less in the HNSCC cell lines and lowest in the OC cell lines. Radiation resistance correlated to the absolute level of released VEGF after irradiation as well as to its relative increase (r>0.9, p<0.01). bFGF levels were not correlated to resistance. VEGF and all three VEGF-receptors were detected in all cell lines analyzed supporting the concept of an autocrine protective mechanism. We suggest that tumor cell survival after irradiation may be enhanced by released VEGF and that the level of released VEGF directly corresponds to the resistance of the tumor to irradiation.
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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