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.
Roodman
G David
GD
Bone Biology Center, University of Pittsburgh Medical Center, University of Pittsburgh, PA 15261, USA.
Choi
Sun Jin
SJ
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001847:Bone Diseases / Q000473:pathology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008954:Models, Biological; D009101:Multiple Myeloma / Q000378:metabolism*; D010010:Osteoclasts / Q000502:physiology; D011379:Prognosis
D014408:Biomarkers, Tumor; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; C008718:osteoclast activating factor