RAS Helping RAS

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Science  15 Mar 2013:
Vol. 339, Issue 6125, pp. 1253-1255
DOI: 10.1126/science.339.6125.1253-e

Solid tumors contain not only malignant cells but also a wide array of host-derived cells that can have dramatic effects on tumor behavior. These include macrophages, immune cells that enhance tumor progression in part by promoting inflammation and whose presence in tumors correlates with reduced patient survival times. Macrophages must be continually replenished as the tumor grows, but little is known about this replenishment process.

Studying mice bearing lung cancers produced by activation of the RAS oncogene, Cortez-Retamozo et al. found that tumor-associated macrophages are supplied by the spleen, through amplification of hematopoietic stem cells and macrophage progenitor cells. This cell amplification process was stimulated by angiotensin II, a peptide hormone better known for its role in the renin-angiotensin system (RAS), which regulates blood pressure. Notably, mice treated with the blood pressure medication enalapril, which inhibits angiotensin II production, had fewer tumor-associated macrophages and fewer lung tumor nodules than control mice. Whether these results can be extrapolated to human lung cancer remains to be determined.

Immunity 38, 296 (2013).

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