MIP-1 alpha and myeloma bone disease.

Figure 5 is a proposed model for MIP-1alpha's effects on myeloma bone disease. MIP-1alpha is produced by myeloma cells and directly stimulates OCL formation. In addition MIP-1alpha enhances adhesive interactions between myeloma cells and marrow stromal cells increasing expression of RANKL and IL-6, which further increase bone destruction and tumor burden. The recent evidence from our group and others lead to the conclusion that MIP-1alpha is an important mediator in the debilitating bone destruction in multiple myeloma. Blocking MIP-1alpha expression may have profound effects on myeloma cell growth, homing, and bone destruction in this in vivo model of myeloma. These data suggest that antagonists that decrease MIP-1alpha activity in vivo or blocking MIP-1alpha signaling by neutralizing its receptor may provide therapeutic alternatives for treating patients with myeloma to decrease both their tumor burden and bone destruction.