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

Michael Quante; Shui Ping Tu; Hiroyuki Tomita; Tamas Gonda; Sophie S.W. Wang; Shigeo Takashi; Gwang Ho Baik; Wataru Shibata; Bethany DiPrete; Kelly S. Betz; Richard Friedman; Andrea Varro; Benjamin Tycko; Timothy C. Wang

doi:10.1016/j.ccr.2011.01.020

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

Michael Quante, Shui Ping Tu, Hiroyuki Tomita, Tamas Gonda, Sophie S.W. Wang, Shigeo Takashi, Gwang Ho Baik, Wataru Shibata, Bethany DiPrete, Kelly S. Betz, Richard Friedman, Andrea Varro, Benjamin Tycko, Timothy C. Wang

Research output: Contribution to journal › Article › peer-review

869 Scopus citations

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.

Original language	English
Pages (from-to)	257-272
Number of pages	16
Journal	Cancer Cell
Volume	19
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2011.01.020
State	Published - 15 Feb 2011
Externally published	Yes

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@article{bcf8e3a24c3c4937ba6918f0c7a0719e,

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.",

author = "Michael Quante and Tu, {Shui Ping} and Hiroyuki Tomita and Tamas Gonda and Wang, {Sophie S.W.} and Shigeo Takashi and Baik, {Gwang Ho} and Wataru Shibata and Bethany DiPrete and Betz, {Kelly S.} and Richard Friedman and Andrea Varro and Benjamin Tycko and Wang, {Timothy C.}",

note = "Funding Information: We would like to thank D. Brenner and S. Magness for the generous gift of αSMA-RFP and collagen-α1-GFP mice, H. Nakagawa for instructing in organotypic culture, P. Good for excellent technical assistance, A. Whelan and J. DeGrazia for managing the mouse colony, R. Chen for help with IHC, K. Novak for critical reading and editing of the manuscript, and all members of the T.C.W. laboratory for helpful comments and discussion. T.C.W. is supported by National Institutes of Health grants 1U54CA126513, RO1CA093405, and R01CA120979. M.Q. is supported by a grant from the Mildred-Scheel-Stiftung, Deutsche Krebshilfe, Germany. W.S. is supported by the Japan Society for the Promotion of Science 2009. S.T. is supported NIH grant R21CA149865. ",

year = "2011",

month = feb,

day = "15",

doi = "10.1016/j.ccr.2011.01.020",

language = "English",

volume = "19",

pages = "257--272",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "2",

}

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.

N1 - Funding Information: We would like to thank D. Brenner and S. Magness for the generous gift of αSMA-RFP and collagen-α1-GFP mice, H. Nakagawa for instructing in organotypic culture, P. Good for excellent technical assistance, A. Whelan and J. DeGrazia for managing the mouse colony, R. Chen for help with IHC, K. Novak for critical reading and editing of the manuscript, and all members of the T.C.W. laboratory for helpful comments and discussion. T.C.W. is supported by National Institutes of Health grants 1U54CA126513, RO1CA093405, and R01CA120979. M.Q. is supported by a grant from the Mildred-Scheel-Stiftung, Deutsche Krebshilfe, Germany. W.S. is supported by the Japan Society for the Promotion of Science 2009. S.T. is supported NIH grant R21CA149865.

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 - http://www.scopus.com/inward/record.url?scp=79751501829&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2011.01.020

DO - 10.1016/j.ccr.2011.01.020

M3 - Article

C2 - 21316604

AN - SCOPUS:79751501829

SN - 1535-6108

VL - 19

SP - 257

EP - 272

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -

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

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