Malignant Loss of Balance

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Science  12 Oct 2001:
Vol. 294, Issue 5541, pp. 269
DOI: 10.1126/science.294.5541.269a

Multiple myeloma is a generally incurable bone marrow cancer of unknown cause characterized by uncontrolled growth of plasma cells. One of its most prominent clinical features is severe bone destruction caused by overproduction of osteoclasts—the cells that resorb bone during bone remodeling. The interaction between the tumor cells and the marrow stroma is important during osteoclast production, but the underlying molecular mechanism has been unclear.

Pearse et al. show that multiple myeloma deregulates osteoclast production by disrupting the balance between TRANCE, a tumor necrosis factor-related cytokine responsible for osteoclast generation, and its inhibitor, osteoprotegerin (OPG), in the marrow stroma. In mice, TRANCE antagonists reduced myeloma-induced bone destruction and, unexpectedly, also inhibited tumor progression. Thus, bone destruction and tumor cell survival seem to be interdependent processes in multiple myeloma. Therapies that target the TRANCE-OPG cytokine axis are already being developed for treatment of osteoporosis and other bone disorders, and these findings may open up new possibilities for the treatment of multiple myeloma.—PAK

Proc. Natl. Acad. Sci. U.S.A.98, 11581 (2001).

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