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

• Published in: Cancer and metastasis reviews Vol. 33; no. 2-3; pp. 511 - 525
• Main Authors: Cook, Leah M., Shay, Gemma, Aruajo, Arturo, Lynch, Conor C.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2014; Springer; Springer Nature B.V
• Subjects: Adaptive Immunity; Animals; Biomedical and Life Sciences; Biomedicine; Bone Neoplasms - complications; Bone Neoplasms - secondary; Cancer Research; Denosumab; Humans; Immunity, Innate; Male; Metastasis; Models, Biological; Neoplastic Stem Cells - metabolism; Neurons; Oncology; Pain - etiology; Prostatic Neoplasms - etiology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; T cells; Tumor Microenvironment; Vicious cycle; Bone metastasis; Mathematical modeling; Immune cells; Prostate cancer; Stem cells
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-014-9494-4

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.