Journal of Neuro-Oncology

, Volume 104, Issue 1, pp 103–112 | Cite as

Bevacizumab can induce reactivity to VEGF-C and -D in human brain and tumour derived endothelial cells

  • S. Grau
  • J. Thorsteinsdottir
  • L. von Baumgarten
  • F. Winkler
  • J.-C. Tonn
  • C. Schichor
Laboratory Investigation - Human/Animal Tissue

Abstract

Though clinical trials demonstrated effectiveness of the anti-VEGF antibody bevacizumab (Avastin) in adjuvant therapies for some solid tumours, there are rather few experimental data about cellular effects of bevacizumab on tumour cells and tumour associated endothelial cells. Recent reports demonstrate resistance mechanisms and secondary re-angiogenesis after a transient normalization of tumour vessels. Therefore we investigated the influence of bevacizumab on human glioma cells and human brain derived as well as tumour derived endothelial cells focussing on the role of VEGF-C and -D as potential alternative pro-angiogenic factors. Bevacizumab treatment showed no influence on proliferation after short term exposure (1–5 days) but slowed down endothelial cell proliferation by 25–30% after 14 days treatment. There was no significant induction of apoptosis after short or long term exposure. Tube formation capabilities were significantly impaired by bevacizumab with a continuing effect after 14 days of treatment even after omitting the antibody. VEGF-C and -D had no effect on endothelial cells in untreated or short term treatment groups. However, cells developed responsiveness to these factors in terms of increased proliferation and tube formation after 14 days bevacizumab treatment. Furthermore, bevacizumab induced expression of VEGF-C and -D in glioma cells. Treatment with bevacizumab may induce alterations in human brain and tumour endothelial cells leading to escape mechanisms from anti-VEGF therapy. VEGF-C and -D thus might act as alternative pro-angiogenic factors during anti-VEGF therapy.

Keywords

Angiogenesis VEGF VEGF-C VEGF-D Bevacizumab Glioma Endothelial cells 

Notes

Acknowledgment

This study was supported by a grant of the Else-Kroener-Fresenius-Stiftung to F. Winkler and S. Grau and by the grant SFB 824 of the Deutsche Forschungsgemeinschaft (DFG).

Supplementary material

11060_2010_480_MOESM1_ESM.doc (224 kb)
Supplementary material 1 (DOC 224 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • S. Grau
    • 1
    • 2
  • J. Thorsteinsdottir
    • 1
  • L. von Baumgarten
    • 3
  • F. Winkler
    • 3
  • J.-C. Tonn
    • 1
  • C. Schichor
    • 1
  1. 1.Department of NeurosurgeryGrosshadern Hospital, Ludwig-Maximilian UniversityMunichGermany
  2. 2.Department of NeurosurgeryUniversity of CologneCologneGermany
  3. 3.Department of NeurologyGrosshadern Hospital, Ludwig-Maximilian UniversityMunichGermany

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