The anti-angiogenic role of soluble-form VEGF receptor in malignant gliomas

  • Authors:
    • Shingo Takano
    • Eiichi Ishikawa
    • Masahide Matsuda
    • Noriaki Sakamoto
    • Hiroyoshi Akutsu
    • Tetsuya Yamamoto
    • Akira Matsumura
  • View Affiliations

  • Published online on: December 19, 2016     https://doi.org/10.3892/ijo.2016.3810
  • Pages: 515-524
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Abstract

Anti-angiogenic therapy represents a promising, new therapeutic modality for malignant gliomas. The present study was designed to define the malignant glioma cases most suitable for anti-angiogenic therapy and to demonstrate the efficacy of anti-angiogenic therapy using soluble-form Flt1 (sFlt1) gene delivery in mice. In human malignant glioma samples (39 glioblastomas, 21 anaplastic astrocytomas and 4 anaplastic oligoastrocytomas), protein expression of VEGF, and its specific natural inhibitor, sFlt1, as well as vessel architecture were assessed. Among these variables, VEGF >1000 ng/ml, VEGF/sFlt1 ratio >1, vessel density >30, and vessel area >7% were prognostic factors for malignant gliomas. VEGF/sFlt1 ratio >1 was the most powerful prognostic marker for survival in multivariate analysis. The sFlt1 gene was also successfully introduced into U87 glioma cells in vitro, resulting in 31% tumor growth inhibition in vivo. sFlt1-transfected tumor demonstrated high sFlt-1 expression along with diminished vessel density and area compared with the control tumor. In transfected tumor, VEGF expression was decreased in the viable area, but still high in the hypoxic area. sFlt1 and VEGF expression was re-evaluated in vitro using glioma cells under normoxic and hypoxic conditions. For sFlt1-transfected cells, VEGF expression was upregulated, but sFlt1 expression was downregulated, resulting in an increase of VEGF/sFlt1 ratio in hypoxic conditions. We conclude that malignant gliomas with a high VEGF/sFlt1 ratio and large vessel area are good candidates for anti-angiogenic therapy. Soluble Flt1 gene delivery was demonstrated to inhibit glioma growth, but this was limited in hypoxic areas.
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February-2017
Volume 50 Issue 2

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

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Spandidos Publications style
Takano S, Ishikawa E, Matsuda M, Sakamoto N, Akutsu H, Yamamoto T and Matsumura A: The anti-angiogenic role of soluble-form VEGF receptor in malignant gliomas. Int J Oncol 50: 515-524, 2017
APA
Takano, S., Ishikawa, E., Matsuda, M., Sakamoto, N., Akutsu, H., Yamamoto, T., & Matsumura, A. (2017). The anti-angiogenic role of soluble-form VEGF receptor in malignant gliomas. International Journal of Oncology, 50, 515-524. https://doi.org/10.3892/ijo.2016.3810
MLA
Takano, S., Ishikawa, E., Matsuda, M., Sakamoto, N., Akutsu, H., Yamamoto, T., Matsumura, A."The anti-angiogenic role of soluble-form VEGF receptor in malignant gliomas". International Journal of Oncology 50.2 (2017): 515-524.
Chicago
Takano, S., Ishikawa, E., Matsuda, M., Sakamoto, N., Akutsu, H., Yamamoto, T., Matsumura, A."The anti-angiogenic role of soluble-form VEGF receptor in malignant gliomas". International Journal of Oncology 50, no. 2 (2017): 515-524. https://doi.org/10.3892/ijo.2016.3810