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Science  24 Dec 2010:
Vol. 330, Issue 6012, pp. 1725
DOI: 10.1126/science.330.6012.1725-d

Stromal cells (green) accompany metastasizing tumor cells (red).

CREDIT: DUDA ET AL., PROC. NATL. ACAD. SCI. U.S.A. 107, 21677 (2010)

Tumor metastases are a major cause of death from solid tumors. Evidence from preclinical models suggests that tumor cells do not metastasize alone but rather are assisted by specific host cells that modify the microenvironment of the target organ so that it can support the survival and growth of newly arriving tumor cells. Two independent studies of lung metastasis in mice converge on this theme. Kowanetz et al. show that tumor cells secrete granulocyte colony-stimulating factor, a protein that expands and mobilizes bone marrow cells of a specific type called Ly6G+Ly6C+ granulocytes and facilitates their homing into the lung before the arrival of tumor cells. Upon accumulation in the lungs, these granulocytes then secrete proteins that enhance the invasive properties of tumor cells, including matrix metalloproteinases and Bv8, a protein that stimulates tumor cell migration. Duda et al. provide evidence that the stability of circulating metastatic tumor cells is enhanced when they “cotravel” with stromal cells derived from the primary tumor, such as fibroblasts. Once these cellular clumps reach the lung, the stromal cells appear to provide an early growth advantage to the tumor cells. Further exploration of the cells and signaling molecules identified in these studies could lead to therapies that prevent or inhibit metastases.

Proc. Natl. Acad. Sci. U.S.A. 107, 21248; 21677 (2010).

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