Metastatic prostate cancer stem cells (cancer-initiating cells) appear to mimic many of the behaviours normally associated with haematopoietic stem cells (HSC). These cells appear to migrate preferentially to the bone marrow in response to signals normally associated with HSC homing. Prostate cancer stem cells can then hijack HSC bone marrow niches, parasitizing the molecular signals that normally regulate HSC maintenance. This is particularly problematic from a treatment perspective as the stem cell niche signal milieu maintains prostate cancer stem cells in a quiescent state, and this in turn appears to enable prostate cancer stem cells to hide from the immune system and evade chemotherapy.
The ability to study this complex biological relationship, and to rapidly develop/test therapeutics to overcome this often fatal disease, is hampered by the lack of a functional in vitro model of prostate cancer stem cells and the bone marrow niche. Through this PCFA New Concept Grant, Dr Mike Doran's team will translate their extensive work on the development of HSC bone marrow niches to the development of a prostate cancer stem cell niche model – a ‘microniche’.