Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment

  • Authors: Kai Fruth, Stefan Weber, Yunus Okcu, Ruediger Noppens, Klaus U. Klein, Eva Joest, Jana Hedrich, Sebastian Thilemann, Benjamin Pogorzelski, Dimitrios Koutsimpelas, Stefan Fischer, Kerstin Muennemann, Annette Affolter, Ulf R. Heinrich, Christoph Brochhausen, Irene Schmidtmann, Wolf J. Mann, Heinz Schmidberger, Laura M. Schreiber, Juergen Brieger
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  • Published online on: Thursday, January 26, 2012
  • Pages: 1573-1579
  • DOI: 10.3892/or.2012.1654

Abstract

Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), ultrasound and near-infrared spectrometry were used to evaluate tumor vessel integrity. Finally, tumors were explanted and VEGF, basic fibroblast growth factor (bFGF), vessel density, proliferation and apoptotic activity were analyzed by immunohistochemistry. Irradiation caused VEGF release and we found evidence for VEGF-mediated vessel protection. In the tumors derived from the combined treatment, blood volume was decreased, and apoptotic indices were increased. Remarkably, bFGF levels and proliferative indices were also increased. Combined irradiation/anti-VEGF treatment resulted in the desired VEGF depletion and increased tumor cell apoptosis. Nonetheless, bFGF and proliferation also increased, possibly suggesting a compensatory response. The application of additional targeted drugs may help develop more effective SCC treatments.
Journal Cover

May 2012
Volume 27 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

2012 Impact Factor: 2.297
Ranked #36/196 Oncology
(total number of cites)

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APA
Fruth, K., Weber, S., Okcu, Y., Noppens, R., Klein, K., Joest, E., Hedrich, J., Thilemann, S., Pogorzelski, B., Koutsimpelas, D., Fischer, S., Muennemann, K., Affolter, A., Heinrich, U., Brochhausen, C., Schmidtmann, I., Mann, W., Schmidberger, H., Schreiber, L., & Brieger, J. (2012). Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment. Oncology Reports, 27(5), 1573-1579.
MLA
Fruth, Weber, Okcu, Noppens, Klein, Joest, Hedrich, Thilemann, Pogorzelski, Koutsimpelas, Fischer, Muennemann, Affolter, Heinrich, Brochhausen, Schmidtmann, Mann, Schmidberger, Schreiber, and Juergen Brieger. "Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment." Oncology Reports Oncology Reports 27.5 (2012): 1573-1579.
Chicago
Fruth, Weber, Okcu, Noppens, Klein, Joest, Hedrich, Thilemann, Pogorzelski, Koutsimpelas, Fischer, Muennemann, Affolter, Heinrich, Brochhausen, Schmidtmann, Mann, Schmidberger, Schreiber, and Juergen Brieger. "Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment." Oncology Reports Oncology Reports 27 no. 5 (2012): 1573-1579.