Osteoblastogenesis and tumor growth in myeloma.
Myeloma is associated with suppression of osteoblastogenesis, consequentially resulting in increased osteoclast activity and induction of typical osteolytic bone disease. The molecular mechanisms by which myeloma cells suppress osteoblastogenesis and the consequences of increased osteoblast activity on myeloma cell growth have been partially delineated only recently. Reduced osteoblastogenesis is a consequence of abnormal properties and impaired osteogenic potential of osteoprogenitor cells from myeloma patients and is also the result of production of multiple osteoblastogenesis inhibitors by myeloma cells and by microenvironmental cells within the myelomatous bone. Nevertheless, novel osteoblast-activating agents (e.g. proteasome inhibitor bortezomib) are capable of inducing bone formation in myeloma animal models and clinically. These agents induce increased osteoblast activity, often coupled with a concomitant reduction in osteoclastogenesis, that is strongly associated with reduced myeloma tumor burden. In vitro, osteoblasts, in contrast to osteoclasts, attenuate the growth of myeloma cells from a large subset of patients; potential molecular mechanisms are discussed. These studies suggest that myeloma cells suppress osteoblastogenesis to their advantage and that increased osteoblast activity is a promising approach to treat myeloma bone disease and simultaneously control myeloma development and progression.
Yaccoby
Shmuel
S
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. yaccobyshmuel@uams.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011719:Pyrazines / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D001897:Boronic Acids; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011719:Pyrazines; D000069286:Bortezomib