Short-term anti-vascular endothelial growth factor treatment elicits vasculogenic mimicry formation of tumors to accelerate metastasis

J Exp Clin Cancer Res. 2012 Feb 23;31(1):16. doi: 10.1186/1756-9966-31-16.


Background: Antiangiogenic therapy is one of the most significant advances in anticancer treatment. The benefits of antiangiogenic therapies of late-stage cancers have been investigated but are still too limited.

Methods: We used an ovarian cancer model to test the effect of short-term bevacizumab treatment on metastasis as measured by bioluminescence. Western blotting and CD34-PAS dual staining were performed to assess hypoxia-inducible transcription factor-1α (HIF-1α) expression and vasculogenic mimicry(VM) formation. Cell viability was examined by a CCK8 assay.

Results: Bevacizumab demonstrated antitumor effects in models of ovarian cancer, but also accelerated metastasis together, with marked hypoxia and VM formation in mice receiving short-term therapy. Bevacizumab treatment did not affect SKOV3 cell viability and the amount of VM in three-dimensional culture.

Conclusion: These results suggest that antiangiogenic therapy may potentially influence the progression of metastatic disease, which has been linked to the hypoxic response and VM formation.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Bevacizumab
  • Cell Hypoxia
  • Cell Line, Tumor
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Neovascularization, Pathologic* / drug therapy
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / drug therapy
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • Bevacizumab