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Angiogenesis

Alternative pathways

Nature Reviews Cancer volume 5, page 667 (2005)Cite this article

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HIF1, a heterodimeric protein that consists of α and β subunits, is a transcription factor that becomes activated under conditions of low oxygen to upregulate genes that mediate angiogenesis, such as vascular endothelial growth factor (VEGF). Mizukami et al. investigated whether inhibition of HIF1 alone is sufficient to block tumour angiogenesis using HIF1α short infering RNA knockdown in colon cancer cells. Surprisingly, they observed that when the HIF1 knockdown cells were transplanted into mice, the resulting tumours remained highly vascularized. Furthermore, in these tumours, VEGF expression was only reduced by 50%, compared with tumours that expressed wild-type levels of HIF1α. As VEGF levels were reduced but new blood vessels still formed, could there be other angiogenic factors that are upregulated in a compensatory manner to maintain tumour vascularity in the absence of HIF1?

To answer this question, the authors performed gene-expression analysis on hypoxic colon cancer cells. Strikingly, expression of the pro-angiogenic cytokine interleukin-8 (IL-8) was upregulated 2.5-fold in HIF1α knockdown cells, but not in cells that expressed wild-type levels of HIF1α. Furthermore, knockdown of HIF1α in pancreatic, breast and lung cancer cells resulted in a similar induction of IL-8.

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References

ORIGINAL RESEARCH PAPER

  1. Mizukami, Y. et al. Induction of interleukin-8 preserves the angiogenic response in HIF-1 deficient colon cancer cells. Nature Med. 21 Aug 2005 (10.1038/nm1294)

FURTHER READING

  1. Semenza, G. Targeting HIF-1 for cancer therapy. Nature Rev. Cancer 3, 721–732 (2003)

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Authors
  1. Kristine Novak
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Novak, K. Alternative pathways. Nat Rev Cancer 5, 667 (2005). https://doi.org/10.1038/nrc1708

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  • DOI: https://doi.org/10.1038/nrc1708

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