Author/Authors :
Quante، نويسنده , , Michael and Tu، نويسنده , , Shui Ping and Tomita، نويسنده , , Hiroyuki and Gonda، نويسنده , , Tamas and Wang، نويسنده , , Sophie S.W. and Takashi، نويسنده , , Shigeo and Baik، نويسنده , , Gwang Ho and Shibata، نويسنده , , Wataru and DiPrete، نويسنده , , Bethany and Betz، نويسنده , , Kelly S. and Friedman، نويسنده , , Richard and Varro، نويسنده , , Andrea and Tycko، نويسنده , , Benjamin and Wang، نويسنده , , Timothy C.، نويسنده ,
Abstract :
Summary
oma-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.
