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Cancer Cell. 2011 Feb 15;19(2):257-72. doi: 10.1016/j.ccr.2011.01.020.

Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth.

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1
Division of Digestive and Liver Diseases, Columbia University, New York, NY 10025, USA.

Abstract

Carcinoma-associated fibroblasts (CAFs) that express α-smooth muscle actin (αSMA) contribute to cancer progression, but their precise origin and role are unclear. Using mouse models of inflammation-induced gastric cancer, we show that at least 20% of CAFs originate from bone marrow (BM) and derive from mesenchymal stem cells (MSCs). αSMA+ myofibroblasts (MFs) are niche cells normally present in BM and increase markedly during cancer progression. MSC-derived CAFs that are recruited to the dysplastic stomach express IL-6, Wnt5α and BMP4, show DNA hypomethylation, and promote tumor growth. Moreover, CAFs are generated from MSCs and are recruited to the tumor in a TGF-β- and SDF-1α-dependent manner. Therefore, carcinogenesis involves expansion and relocation of BM-niche cells to the tumor to create a niche to sustain cancer progression.

PMID:
21316604
PMCID:
PMC3060401
DOI:
10.1016/j.ccr.2011.01.020
[Indexed for MEDLINE]
Free PMC Article
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