Calcified Tissue International

, Volume 102, Issue 2, pp 152–162 | Cite as

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

  • Sun H. Park
  • Evan T. Keller
  • Yusuke Shiozawa


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.


Prostate cancer Bone metastasis Bone-targeted therapy Bone marrow microenvironment Skeletal complications 



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.

Conflict of interest

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


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Cancer Biology and Comprehensive Cancer CenterWake Forest School of MedicineWinston-SalemUSA
  2. 2.Departments of Urology and PathologyUniversity of Michigan Medical SchoolAnn ArborUSA

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