Vessel co-option in cancer

Abstract

All solid tumours require a vascular supply in order to progress. Although the ability to induce angiogenesis (new blood vessel growth) has long been regarded as essential to this purpose, thus far, anti-angiogenic therapies have shown only modest efficacy in patients. Importantly, overshadowed by the literature on tumour angiogenesis is a long-standing, but continually emerging, body of research indicating that tumours can grow instead by hijacking pre-existing blood vessels of the surrounding nonmalignant tissue. This process, termed vessel co-option, is a frequently overlooked mechanism of tumour vascularization that can influence disease progression, metastasis and response to treatment. In this Review, we describe the evidence that tumours located at numerous anatomical sites can exploit vessel co-option. We also discuss the proposed molecular mechanisms involved and the multifaceted implications of vessel co-option for patient outcomes.

Key points

  • Vessel co-option is a non-angiogenic process through which tumour cells utilize pre-existing tissue blood vessels to support tumour growth, survival and metastasis.

  • Vessel co-option is identified histologically using the presence of specific morphological features but cannot be discriminated from angiogenesis by examining microvessel density alone.

  • Vessel co-option is adopted by a wide range of human tumours growing within numerous tissues including the brain, liver, lungs and lymph nodes.

  • Mechanisms driving vessel co-option are poorly understood, although tumour cell invasion and tumour cell adhesion pathways are known to be involved.

  • Vessel co-option is implicated in patient outcomes and resistance to cancer therapies and is a legitimate target of new therapeutic strategies.

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Fig. 1: Summary of selected randomized phase III clinical trials evaluating the efficacy of anti-angiogenic agents.
Fig. 2: Historical timeline of selected key developments in vessel co-option and angiogenesis research.
Fig. 3: Tumour growth patterns associated with vessel co-option or angiogenesis in the lung.
Fig. 4: Tumour growth patterns associated with vessel co-option or angiogenesis in the liver.
Fig. 5: Tumour growth patterns associated with vessel co-option or angiogenesis in the brain.
Fig. 6: Potential strategies to inhibit vessel co-option in cancer.

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Acknowledgements

The authors acknowledge financial support provided by Breast Cancer Now (A.R.R.) and Worldwide Cancer Research (R.S.K. and E.A.K.). The authors thank A. Berghoff and M. Preusser (Medical University of Vienna) for providing histopathological images of brain tumours and C. Cheng (University of Toronto) for her secretarial assistance. The authors also thank S. Barry (AstraZeneca) for providing critical comments on the manuscript.

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All authors researched data for this article and made a substantial contribution to discussions of content, E.A.K. and A.R.R. wrote the manuscript, and all authors edited and/or reviewed the manuscript prior to submission.

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Correspondence to Elizabeth A. Kuczynski or Andrew R. Reynolds.

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E.A.K. and A.R.R. are full-time employees of AstraZeneca. R.S.K. has received honoraria from Apobiologix, Boehringer Ingelheim, Merck Pharmaceuticals and Merck Serono. F.P. and P.B.V. declare no competing interests.

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Kuczynski, E.A., Vermeulen, P.B., Pezzella, F. et al. Vessel co-option in cancer. Nat Rev Clin Oncol 16, 469–493 (2019). https://doi.org/10.1038/s41571-019-0181-9

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