Effects of erythropoietin on the bone microenvironment.

It has been well established that blood and bone share a unique, regulatory relationship with one another, though the specifics of this relationship still remain unanswered. Erythropoietin (Epo) is known primarily for its role as a hematopoietic hormone. However, after the discovery of Epo receptor outside the hematopoietic tissues, Epo has been avidly studied for its possible nonhematopoietic effects. It has been proposed that Epo interacts with bone both directly, by activating bone marrow stromal cells, and indirectly, through signaling pathways on hematopoietic stem cells. Yet, the role of Epo in regulating skeletal maintenance and regeneration remains controversial. Here, we review the current state of knowledge pertaining to the effects of Epo on the skeleton.

The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites.

In post-fetal life, hematopoiesis occurs in unique microenvironments or 'niches' in the marrow. Niches facilitate the maintenance of hematopoietic stem cells (HSCs) as unipotent, while supporting lineage commitment of the expanding blood populations. As the physical locale that regulates HSC function, the niche function is vitally important to the survival of the organism. This places considerable selective pressure on HSCs, as only those that are able to engage the niche in the appropriate context are likely to be maintained as stem cells. Since niches are central regulators of stem cell function, it is not surprising that molecular parasites like neoplasms are likely to seek out opportunities to harvest resources from the niche environment. As such, the niche may unwittingly participate in tumorigenesis as a leukemic or neoplastic niche. The niche may also promote metastasis or chemo-resistance of hematogenous neoplasms or solid tumors. This review focuses on what is known about the physical structures of the niche, how the niche participates in hematopoiesis and neoplastic growth and what molecules are involved. Further understanding of the interactions between stem cells and the niche may be useful for developing therapeutic strategies.

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis.

BACKGROUND: The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. RESULTS: Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. CONCLUSION: Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes.