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Tumour innervation and neurosignalling in prostate cancer

Nature Reviews Urology volume 17, pages 119–130 (2020)Cite this article

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Abstract

Prostate cancer progression has been shown to be dependent on the development of autonomic nerves into the tumour microenvironment. Sympathetic nerves activate adrenergic neurosignalling that is necessary in early stages of tumour progression and for initiating an angiogenic switch, whereas parasympathetic nerves activate cholinergic neurosignalling resulting in tumour dissemination and metastasis. The innervation of prostate cancer seems to be initiated by neurotrophic growth factors, such as the precursor to nerve growth factor secreted by tumour cells, and the contribution of brain-derived neural progenitor cells has also been reported. Current experimental, epidemiological and clinical evidence shows the stimulatory effect of tumour innervation and neurosignalling in prostate cancer. Using nerves and neurosignalling could have value in the management of prostate cancer by predicting aggressive disease, treating localized disease through denervation and relieving cancer-associated pain in bone metastases.

Key points

  • Prostate cancer is infiltrated by autonomic nerves that actively stimulate cancer progression.

  • Autonomic nerves infiltrate the tumour microenvironment in response to tumour-derived neurotrophins and axon guidance molecules.

  • Animal models have demonstrated that adrenergic and cholinergic neurosignalling stimulates prostate cancer progression, angiogenesis, invasion and metastasis. Chemical or surgical denervation, as well as genetic or pharmacological blockade, completely inhibit these effects.

  • Attenuated tumour neurosignalling might be a key factor in the decreased incidence of prostate cancer observed in patients with spinal cord injuries or those taking β-blockers.

  • Nerves and neurotrophic growth factors could be used as biomarkers of clinically aggressive prostate cancer, or as therapeutic targets to prevent cancer progression, dissemination and cancer-induced pain.

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Fig. 1: Innervation and neurosignalling in prostate cancer.

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Acknowledgements

The authors wish to acknowledge the financial support of the Cancer Council, New South Wales, Australia and the National Health and Medical Research Council (NHMRC), Australia.

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Authors and Affiliations

  1. School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia

    Brayden March, Allison Steigler & Jim Denham

  2. Department of Surgery, John Hunter Hospital, New Lambton Heights, NSW, Australia

    Brayden March & Alison Blatt

  3. Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia

    Brayden March, Sam Faulkner, Phillip Jobling & Hubert Hondermarck

  4. School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia

    Sam Faulkner, Phillip Jobling & Hubert Hondermarck

  5. Newcastle Calvary Mater Hospital, Waratah, NSW, Australia

    Allison Steigler & Jim Denham

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B.M. researched data for the article, B.M. and H.H. made substantial contributions to discussion of content and wrote the manuscript, and all authors reviewed and edited the manuscript before submission.

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March, B., Faulkner, S., Jobling, P. et al. Tumour innervation and neurosignalling in prostate cancer. Nat Rev Urol 17, 119–130 (2020). https://doi.org/10.1038/s41585-019-0274-3

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