Tumor stroma interaction leading to the development of lethal phenotypes of human prostate cancer

Reciprocal tumor-stroma interactions between prostate cancer and bone stromal cells are crucial to the colonization and survival of prostate cancer cells in bone. Our ongoing investigations has shown that a number of soluble factors contribute to the interaction between prostate cancer, bone marrow stromal cells, osteoblasts, osteoclasts and vascular endothelial cells. Factors produced by prostate cancer and bone stromal cells could enhance osteoblastogenesis and/or osteoclastogenesis. The resulting activation of these responses could be the molecular basis of preferential prostate cancer homing and colonization in bone. Studying osteomimicry in prostate cancer cells, we identified novel cis-elements, CREs, that are responsible for mediating prostate cancer and bone stroma interaction with c-AMP-dependent PKA pathway, playing a pivotal role in the maintenance of bone-like properties by prostate cancer cells prior to metastasis. We identified a previously-identified factor in myeloma, β2M, as one of the key factors responsible for supporting osteomimicry of prostate cancer cells. By transfecting b2M into human prostate cancer cells, we observed explosive growth of human prostate cancer in bone. Since β2M is expressed by prostate cancer cells and clinical prostate tumors, and by a number of bone homing cancer types, we suggest that β2M is an attractive therapeutic target for the control of human prostate cancer bone metastasis.