title: Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth.
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.
authors.affiliation: Division of Digestive and Liver Diseases, Columbia University, New York, NY 10025, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Quante
authors.forename: Shui Ping
authors.initials: SP
authors.lastname: Tu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomita
authors.forename: Tamas
authors.initials: T
authors.lastname: Gonda
authors.forename: Sophie S W
authors.initials: SS
authors.lastname: Wang
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takashi
authors.forename: Gwang Ho
authors.initials: GH
authors.lastname: Baik
authors.forename: Wataru
authors.initials: W
authors.lastname: Shibata
authors.forename: Bethany
authors.initials: B
authors.lastname: Diprete
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Betz
authors.forename: Richard
authors.initials: R
authors.lastname: Friedman
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tycko
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation; D016207:Cytokines
chemical_list: D000199:Actins; D036341:Intercellular Signaling Peptides and Proteins; D019718:Receptors, CXCR4; D016212:Transforming Growth Factor beta; C514936:CXCR4 protein, mouse; C544013:alpha-smooth muscle actin, mouse; C113178:Grem1 protein, mouse; D016207:Cytokines