Hematopoietic Stem Cell Niche Is a Potential Therapeutic Target for Bone Metastatic Tumors

Despite significant improvements in therapy, the prognosis for cancer with bone metastasis is generally poor. Therefore, there is a great need for new therapeutic approaches for metastatic disease. It has been appreciated that tumor cells metastasize to bone using mechanisms similar to those of hematopoietic stem cells (HSC) homing to bone marrow (e.g., CXCL12/CXCR4). It was recently found that prostate cancer cells target the bone marrow microenvironment for HSCs, or the HSC niche, during metastasis. Of importance, these disseminated prostate cancer cells can be mobilized out of the niche with the use of HSC mobilizing agents. These findings suggest that the bone marrow HSC niche is a potential therapeutic target for metastatic disease. Therefore, a hypothesis worth considering is that agents that can disrupt the interactions between tumor cells and the HSC niche may be efficacious when used in conjunction with standard chemotherapeutic agents. Although further understanding of the tumor-niche interactions is needed, the concept of targeting the niche in conjunction with chemotherapy could open up new possibilities to eradicate incurable metastatic diseases. Clin Cancer Res; 17(17); 5553-8. (C) 2011 AACR.