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Pericytes on the Tumor Vasculature: Jekyll or Hyde?

  • Review Paper
  • Published:
Cancer Microenvironment

Abstract

The induction of tumor vasculature, known as the ‘angiogenic switch’, is a rate-limiting step in tumor progression. Normal blood vessels are composed of two distinct cell types: endothelial cells which form the channel through which blood flows, and mural cells, the pericytes and smooth muscle cells which serve to support and stabilize the endothelium. Most functional studies have focused on the responses of endothelial cells to pro-angiogenic stimuli; however, there is mounting evidence that the supporting mural cells, particularly pericytes, may play key regulatory roles in both promoting vessel growth as well as terminating vessel growth to generate a mature, quiescent vasculature. Tumor vessels are characterized by numerous structural and functional abnormalities, including altered association between endothelial cells and pericytes. These dysfunctional, unstable vessels contribute to hypoxia, interstitial fluid pressure, and enhanced susceptibility to metastatic invasion. Increasing evidence points to the pericyte as a critical regulator of endothelial activation and subsequent vessel development, stability, and function. Here we discuss both the stimulatory and inhibitory effects of pericytes on the vasculature and the possible utilization of vessel normalization as a therapeutic strategy to combat cancer.

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Acknowledgements

The work of LJMB is supported by Public Health Service grant CA138727 from the National Institutes of Health. AS was supported by NIH T32 CA113267. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Authors and Affiliations

  1. Department of Radiation Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA

    Keith D. Barlow, Anne M. Sanders & Linda J. Metheny-Barlow

  2. Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA

    Keith D. Barlow & Linda J. Metheny-Barlow

  3. Wake Forest Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA

    Shay Soker & Linda J. Metheny-Barlow

  4. Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA

    Shay Soker

  5. Institute of Anatomy and Cell Biology, Julius-Maximilians-University Wuerzburg, Wuerzburg, Germany

    Suleyman Ergun

Authors
  1. Keith D. Barlow
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  2. Anne M. Sanders
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  3. Shay Soker
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  4. Suleyman Ergun
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  5. Linda J. Metheny-Barlow
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Corresponding author

Correspondence to Linda J. Metheny-Barlow.

Additional information

Kalluri and colleagues recently provide evidence that decreased pericyte coverage of the tumor vasculature is associated with distant metastases and shorter disease-free survival of breast cancer patients. Further, they demonstrated that ablation of pericytes is associated with increased metastasis to lung in an orthotopic mouse model of breast cancer. Cooke et al., Cancer Cell 21:66–81, 2012.

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Barlow, K.D., Sanders, A.M., Soker, S. et al. Pericytes on the Tumor Vasculature: Jekyll or Hyde?. Cancer Microenvironment 6, 1–17 (2013). https://doi.org/10.1007/s12307-012-0102-2

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  • DOI: https://doi.org/10.1007/s12307-012-0102-2

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