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

被引：1127

作者：

Quante, Michael ^{[1
]}

Tu, Shui Ping ^{[1
,6
]}

Tomita, Hiroyuki ^{[1
]}

Gonda, Tamas ^{[1
,2
,3
]}

Wang, Sophie S. W. ^{[1
]}

Takashi, Shigeo ^{[1
]}

Baik, Gwang Ho ^{[1
]}

Shibata, Wataru ^{[1
]}

DiPrete, Bethany ^{[1
]}

Betz, Kelly S. ^{[1
]}

Friedman, Richard ^{[4
]}

Varro, Andrea ^{[5
]}

Tycko, Benjamin ^{[2
,3
]}

Wang, Timothy C. ^{[1
]}

机构：

[1] Columbia Univ, Div Digest & Liver Dis, New York, NY 10025 USA

[2] Columbia Univ, Inst Canc Genet, New York, NY 10025 USA

[3] Columbia Univ, Dept Pathol, New York, NY 10025 USA

[4] Columbia Univ, Dept Biomed Informat, New York, NY 10025 USA

[5] Univ Liverpool, Sch Biomed Sci, Dept Physiol Lab, Liverpool L69 3BX, Merseyside, England

[6] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, Susan L Cullman Lab Canc Res,Ctr Canc Prev Res, Piscataway, NJ 08854 USA

来源：

CANCER CELL | 2011年 / 19卷 / 02期

基金：

美国国家卫生研究院; 日本学术振兴会;

关键词：

GASTRIC-CANCER; EPITHELIAL-CELLS; STROMAL CELLS; FIBROBLASTS; DIFFERENTIATION; INFLAMMATION; TRANSPLANTATION; OVEREXPRESSION; ANGIOGENESIS; PARADIGM;

D O I：

10.1016/j.ccr.2011.01.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Carcinoma-associated fibroblasts (CAFs) that express alpha-smooth muscle actin (alpha SMA) 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). alpha SMA+ 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, Wnt5 alpha and BMP4, show DNA hypomethylation, and promote tumor growth. Moreover, CAFs are generated from MSCs and are recruited to the tumor in a TGF-beta- and SDF-1 alpha-dependent manner. Therefore, carcinogenesis involves expansion and relocation of BM-niche cells to the tumor to create a niche to sustain cancer progression.

引用

页码：257 / 272

页数：16

共 38 条

[1]

ALLINEN M, 2004, BLOOD, V6, P4341

[2]

Gastrointestinal stem cells in development and cancer [J].

Brabletz, S. ;

Schmalhofer, O. ;

Brabletz, T. .

JOURNAL OF PATHOLOGY, 2009, 217 (02) :307-317

[3]

Inflammation and cancer [J].

Coussens, LM ;

Werb, Z .

NATURE, 2002, 420 (6917) :860-867

[4]

Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts [J].

Direkze, NC ;

Hodivala-Dilke, K ;

Jeffery, R ;

Hunt, T ;

Poulsom, R ;

Oukrif, D ;

Alison, MR ;

Wright, NA .

CANCER RESEARCH, 2004, 64 (23) :8492-8495

[5]

Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone-marrow-tranplanted mice [J].

Direkze, NC ;

Forbes, SJ ;

Brittan, M ;

Hunt, T ;

Jeffery, R ;

Preston, SL ;

Poulsom, R ;

Hodivala-Dilke, K ;

Alison, MR ;

Wright, NA .

STEM CELLS, 2003, 21 (05) :514-520

[6]

Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-κB-Dependent Manner [J].

Erez, Neta ;

Truitt, Morgan ;

Olson, Peter ;

Hanahan, Douglas .

CANCER CELL, 2010, 17 (02) :135-147

[7]

IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated Cancer [J].

Grivennikov, Sergei ;

Karin, Eliad ;

Terzic, Janos ;

Mucida, Daniel ;

Yu, Guann-Yi ;

Vallabhapurapu, Sivakumar ;

Scheller, Juergen ;

Rose-John, Stefan ;

Cheroutre, Hilde ;

Eckmann, Lars ;

Karin, Michael .

CANCER CELL, 2009, 15 (02) :103-113

[8]

Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer [J].

Guo, Xiaoying ;

Oshima, Hiroko ;

Kitmura, Takanori ;

Taketo, Makoto M. ;

Oshima, Masanobu .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (28) :19864-19871

[9]

Hayward SW, 2001, CANCER RES, V61, P8135

[10]

Helicobacter pylori and gastric cancer:: A new paradigm for inflammation-associated epithelial cancers [J].

Houghton, J ;

Wang, TC .

GASTROENTEROLOGY, 2005, 128 (06) :1567-1578

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