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Bone Marrow Microenvironment as a Regulator and Therapeutic Target for Prostate Cancer Bone Metastasis

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Abstract

Bone is the most common site of prostate cancer metastasis. Once prostate cancer cells metastasize to bone, the mortality rate of prostate cancer patients increases significantly. Furthermore, bone metastases produce multiple skeletal complications, including bone pain that impairs the patients’ quality of life. Effective therapies for bone metastatic disease are underdeveloped with most current therapies being primarily palliative with modest survival benefit. Although the exact mechanisms through which prostate cancer metastasizes to bone are unclear, growing evidence suggests that the bone marrow microenvironment, particularly its hematopoietic activity, is a significant mediator of prostate cancer bone tropism. Moreover, the bone microenvironment may regulate metastatic prostate cancer cells between dormant and proliferative states. In this review, we discuss (1) how prostate cancer cells interact with the bone microenvironment to establish bone metastases and (2) current and future potential treatments for prostate cancer patients with bone metastases.

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Acknowledgements

This work is directly supported by National Cancer Institute Grants CA163124 (Y. Shiozawa) and P01 CA093900 (E. Keller), Department of Defense (W81XWH-14-1-0403 and W81XWH-17-1-0541, Y. Shiozawa), the Wake Forest School of Medicine Internal Pilot Funding (Y. Shiozawa), and the Wake Forest Baptist Comprehensive Cancer Center Internal Pilot Funding (Y. Shiozawa). Y Shiozawa is supported as the Translational Research Academy which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR001420. This work is also supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

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  1. Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Sun H. Park & Yusuke Shiozawa

  2. Departments of Urology and Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA

    Evan T. Keller

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Sun H. Park, Evan T. Keller, and Yusuke Shiozawa declare that they have no conflicts of interest.

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Park, S.H., Keller, E.T. & Shiozawa, Y. Bone Marrow Microenvironment as a Regulator and Therapeutic Target for Prostate Cancer Bone Metastasis. Calcif Tissue Int 102, 152–162 (2018). https://doi.org/10.1007/s00223-017-0350-8

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