Vascular endothelial growth factor is an autocrine survival factor for breast tumour cells under hypoxia

  • Authors:
    • Martin P. Barr
    • David J. Bouchier-Hayes
    • Judith J. Harmey
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/ijo.32.1.41
  • Pages: 41-48
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Abstract

Vascular endothelial growth factor (VEGF) is produced by most tumour types and stimulates the growth of new blood vessels in the tumour. The expansion of a solid tumour ultimately leads to the development of hypoxic regions, which increases VEGF production and further angiogenesis. In this study, we examined the role of VEGF in the survival of breast tumour cells under hypoxia. Murine 4T1 and human MDA-MB-231 tumour cells were cultured under normoxic and hypoxic growth conditions in the presence or absence of VEGF neutralising antibodies. Apoptosis was assessed in addition to changes in expression of the anti- and pro-apoptotic proteins, Bcl-2 and Bad, respectively. The effect of hypoxia on the novel VEGF receptor, NP1 (neuropilin-1) and the role of the PI3K (phosphatidylinositol-3-kinase) signalling pathway in response to VEGF were examined. VEGF blockade resulted in direct tumour cell apoptosis of both tumour cell lines under normoxia and hypoxia. While blocking VEGF resulted in a downregulation of hypoxia-induced Bcl-2 expression, there was a significant increase in the pro-apoptotic protein Bad relative to cells cultured under hypoxia alone. Both hypoxia and VEGF phosphorylated Akt. Neutralising antibodies to VEGF abrogated this effect, implicating the PI3K pathway in VEGF-mediated cell survival of mammary adenocarcinoma cells. This study demonstrates that VEGF acts as a survival factor not only for endothelial cells as previously thought, but also for some breast tumour cells, protecting them from apoptosis, particularly under hypoxic stress. The data presented provide an additional rationale for combining anti-VEGF strategies with conventional anti-cancer therapies such as chemotherapy and radiotherapy.

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January 2008
Volume 32 Issue 1

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

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Spandidos Publications style
Barr MP, Bouchier-Hayes DJ and Harmey JJ: Vascular endothelial growth factor is an autocrine survival factor for breast tumour cells under hypoxia. Int J Oncol 32: 41-48, 2008
APA
Barr, M.P., Bouchier-Hayes, D.J., & Harmey, J.J. (2008). Vascular endothelial growth factor is an autocrine survival factor for breast tumour cells under hypoxia. International Journal of Oncology, 32, 41-48. https://doi.org/10.3892/ijo.32.1.41
MLA
Barr, M. P., Bouchier-Hayes, D. J., Harmey, J. J."Vascular endothelial growth factor is an autocrine survival factor for breast tumour cells under hypoxia". International Journal of Oncology 32.1 (2008): 41-48.
Chicago
Barr, M. P., Bouchier-Hayes, D. J., Harmey, J. J."Vascular endothelial growth factor is an autocrine survival factor for breast tumour cells under hypoxia". International Journal of Oncology 32, no. 1 (2008): 41-48. https://doi.org/10.3892/ijo.32.1.41