Runaway Remodeling

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Science  09 Apr 2010:
Vol. 328, Issue 5975, pp. 139
DOI: 10.1126/science.328.5975.139-c

Bone building (red) by osteoblasts.

CREDIT: VALLET ET AL., PNAS 107, 5124 (2010)

Bone metastases are a common feature of many advanced-stage cancers and are among the most painful and debilitating complications. Tumor cells alter bone tissue by unbalancing the bone remodeling process that occurs naturally throughout adult life. In the context of osteolytic (bone-destroying) metastases, this disruption occurs through an enhanced production of osteoclasts—the cells that resorb bone—or through a suppressed production of osteoblasts—the cells that build bone. The molecular mechanism by which tumor cells alter the abundance of these cell types is the subject of two recent studies using mouse models of cancer.

Vallet et al. found that multiple myeloma cells cause bone marrow stromal cells to secrete activin A, which is a member of the transforming growth factor–β family of cytokines and which inhibits the differentiation of cells into osteoblasts. In independent work on breast cancer–associated bone disease, Min et al. found that Tie2, a receptor tyrosine kinase that is expressed at high levels in breast cancer, is also expressed in bone marrow cells that normally differentiate into osteoclasts and is in fact required for osteoclast production. Inhibition of either activin A or Tie2 signaling with soluble decoy receptors led to the amelioration of osteolytic bone disease, suggesting that these two molecules may be useful therapeutic targets.

Proc. Natl. Acad. Sci. U.S.A. 107, 5124 (2010); Cancer Res. 70, 2819 (2010).

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