Cancer and Metastasis Reviews

, Volume 33, Issue 2–3, pp 511–525 | Cite as

Integrating new discoveries into the “vicious cycle” paradigm of prostate to bone metastases

  • Leah M. Cook
  • Gemma Shay
  • Arturo Aruajo
  • Conor C. LynchEmail author


In prostate to bone metastases, the “vicious cycle” paradigm has been traditionally used to illustrate how metastases manipulate the bone forming osteoblasts and resorbing osteoclasts in order to yield factors that facilitate growth and establishment. However, recent advances have illustrated that the cycle is far more complex than this simple interpretation. In this review, we will discuss the role of exosomes and hematopoietic/mesenchymal stem/stromal cells (MSC) that facilitate the establishment and activation of prostate metastases and how cells including myeloid-derived suppressor cells, macrophages, T cells, and nerve cells contribute to the momentum of the vicious cycle. The increased complexity of the tumor–bone microenvironment requires a system level approach. The evolution of computational models to interrogate the tumor–bone microenvironment is also discussed, and the application of this integrated approach should allow for the development of effective therapies to treat and cure prostate to bone metastases.


Prostate cancer Bone metastasis Stem cells Immune cells Mathematical modeling Vicious cycle 



This work was supported in part by RO1CA143094 (CCL).

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Leah M. Cook
    • 1
  • Gemma Shay
    • 1
  • Arturo Aruajo
    • 2
  • Conor C. Lynch
    • 1
    Email author
  1. 1.Department of Tumor BiologyMoffitt Cancer Center and Research InstituteTampaUSA
  2. 2.Department Integrated Mathematical OncologyMoffitt Cancer Center and Research InstituteTampaUSA

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