Bone Marrow-Derived Myofibroblasts Contribute to the Mesenchymal Stem Cell Niche and Promote Tumor Growth

TY - JOUR

T1 - Bone Marrow-Derived Myofibroblasts Contribute to the Mesenchymal Stem Cell Niche and Promote Tumor Growth

AU - Quante, Michael

AU - Tu, Shui Ping

AU - Tomita, Hiroyuki

AU - Gonda, Tamas

AU - Wang, Sophie S.W.

AU - Takashi, Shigeo

AU - Baik, Gwang Ho

AU - Shibata, Wataru

AU - DiPrete, Bethany

AU - Betz, Kelly S.

AU - Friedman, Richard

AU - Varro, Andrea

AU - Tycko, Benjamin

AU - Wang, Timothy C.

PY - 2011/2/15

Y1 - 2011/2/15

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/79751501829

U2 - 10.1016/j.ccr.2011.01.020

DO - 10.1016/j.ccr.2011.01.020

M3 - Article

C2 - 21316604

SN - 1535-6108

VL - 19

SP - 257

EP - 272

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -