Impact of prostate cancer stem cell niches on prostate cancer tumorigenesis and progression

It has become increasingly clear that prostate cancer stem cells (PCSCs) play essential roles in prostate cancer (PC) initiation, metastasis, and resistance to therapies. However, the underlying mechanisms underpinning this relationship remain unclear. This is partly attributable to our incomplete understanding on niche that supports and regulates PCSCs. In vivo, the capacity of PCSCs in disease initiation and their plasticity in driving PC progression, i.e., metastasis and therapy resistance, are maintained and developed through cues received from niches. Respectively, the according actions of PCSCs in directing the PC course are also regulated by niche. Prostate cancer predominantly metastasizes to the bone. Although metastatic PCs show a good response to the standard of care (androgen deprivation therapy/ADR), resistance inevitably develops in the form of castration-resistant prostate cancer (CRPC) to which therapeutic options are limited. CRPC remains the primary cause of PC death. Overt metastasis to the bone thus marks the lethal progression of the disease. Niches at bone marrow offer complex environment to reserve hematopoietic stem cells (HSCs) quiescence and maintain HSCs active for blood production. PCSCs which seed to bone marrow employ these niche properties using the same mechanisms by which HSCs use in their homing to the niche, initiation of dormancy to survive and subsequently exit from dormancy for metastatic outgrowth. In this chapter, we will systemically review the current understanding of the niche contributions to PCSCs-mediated disease initiation and metastasis to the bone. Limitations, future development, and therapeutic potentials will be discussed.