Home LiteratureArticle Details
PMID: 21316604 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth.

Cancer cell ·Vol. 19 ·No. 2 ·2011-02-15 ·Pages 257-72

Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takashi S, Baik GH, Shibata W, Diprete B, Betz KS, Friedman R, Varro A, Tycko B, Wang TC

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.

MeSH Terms
Actins/metabolism Animals Bone Marrow Cells/cytology Cell Division Cell Transformation, Neoplastic Disease Models, Animal Intercellular Signaling Peptides and Proteins/metabolism Mesenchymal Stem Cells/cytology Mice Neoplasms, Experimental/metabolism,pathology Receptors, CXCR4/metabolism Stomach Neoplasms/metabolism,pathology Transforming Growth Factor beta/metabolism Up-Regulation
Chemicals
Actins CXCR4 protein, mouse Grem1 protein, mouse Intercellular Signaling Peptides and Proteins Receptors, CXCR4 Transforming Growth Factor beta alpha-smooth muscle actin, mouse
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Quante Michael
Division of Digestive and Liver Diseases, Columbia University, New York, NY 10025, USA.
Tu Shui Ping
Tomita Hiroyuki
Gonda Tamas
Wang Sophie S W
Takashi Shigeo
Baik Gwang Ho
Shibata Wataru
Diprete Bethany
Betz Kelly S
Friedman Richard
Varro Andrea
Tycko Benjamin
Wang Timothy C
References (42)
42 references, click to expand
  1. Bone marrow lacks a transplantable progenitor for smooth muscle type alpha-actin-expressing cells.
    Stem Cells. 2006 Jan;24(1):13-22 PMID: 16099999
  2. Asymmetric and symmetric stem-cell divisions in development and cancer.
    Nature. 2006 Jun 29;441(7097):1068-74 PMID: 16810241
  3. BMP signaling and stem cell regulation.
    Dev Biol. 2005 Aug 1;284(1):1-11 PMID: 15963490
  4. Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction.
    Biochem Biophys Res Commun. 2003 Sep 12;309(1):232-40 PMID: 12943687
  5. Human gastrointestinal neoplasia-associated myofibroblasts can develop from bone marrow-derived cells following allogeneic stem cell transplantation.
    Stem Cells. 2009 Jun;27(6):1463-8 PMID: 19492298
  6. Global hypomethylation of genomic DNA in cancer-associated myofibroblasts.
    Cancer Res. 2008 Dec 1;68(23):9900-8 PMID: 19047171
  7. Long-term in vitro expansion alters the biology of adult mesenchymal stem cells.
    Cancer Res. 2008 Jun 1;68(11):4229-38 PMID: 18519682
  8. Host origin of marrow stromal cells following allogeneic bone marrow transplantation.
    Nature. 1987 Jul 30-Aug 5;328(6129):429-32 PMID: 2886914
  9. Inhibition of gastric carcinogenesis by the hormone gastrin is mediated by suppression of TFF1 epigenetic silencing.
    Gastroenterology. 2011 Mar;140(3):879-91 PMID: 21111741
  10. The functional interplay between EGFR overexpression, hTERT activation, and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induces tumor development, invasion, and differentiation.
    Genes Dev. 2007 Nov 1;21(21):2788-803 PMID: 17974918
  11. Gastric cancer originating from bone marrow-derived cells.
    Science. 2004 Nov 26;306(5701):1568-71 PMID: 15567866
  12. Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation.
    Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14842-7 PMID: 17003113
  13. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion.
    Cell. 2005 May 6;121(3):335-48 PMID: 15882617
  14. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts.
    Cancer Res. 2004 Dec 1;64(23):8492-5 PMID: 15574751
  15. Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner.
    Cancer Cell. 2010 Feb 17;17(2):135-47 PMID: 20138012
  16. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice.
    Cancer Cell. 2008 Nov 4;14(5):408-19 PMID: 18977329
  17. Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells.
    Cell. 2010 Oct 1;143(1):134-44 PMID: 20887898
  18. A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations.
    Hepatology. 2004 Nov;40(5):1151-9 PMID: 15389867
  19. Molecular characterization of the tumor microenvironment in breast cancer.
    Cancer Cell. 2004 Jul;6(1):17-32 PMID: 15261139
  20. Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone-marrow-transplanted mice.
    Stem Cells. 2003;21(5):514-20 PMID: 12968105
  21. Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma.
    Cancer. 2002 Dec 15;95(12):2546-54 PMID: 12467069
  22. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.
    Nature. 2010 Aug 12;466(7308):829-34 PMID: 20703299
  23. Normal human colonic subepithelial myofibroblasts enhance epithelial migration (restitution) via TGF-beta3.
    Am J Physiol. 1999 May;276(5):G1087-93 PMID: 10329998
  24. A transient niche regulates the specification of Drosophila intestinal stem cells.
    Science. 2010 Jan 8;327(5962):210-3 PMID: 20056890
  25. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells.
    Cancer Res. 2008 Jun 1;68(11):4331-9 PMID: 18519693
  26. Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin.
    J Cell Sci. 2004 Mar 1;117(Pt 7):1269-80 PMID: 14996946
  27. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.
    Nat Cell Biol. 2010 May;12(5):468-76 PMID: 20418870
  28. Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer.
    J Biol Chem. 2008 Jul 11;283(28):19864-71 PMID: 18495668
  29. Malignant transformation in a nontumorigenic human prostatic epithelial cell line.
    Cancer Res. 2001 Nov 15;61(22):8135-42 PMID: 11719442
  30. Fibroblastic colony-forming unit bone marrow cells delay progression to gastric dysplasia in a helicobacter model of gastric tumorigenesis.
    Stem Cells. 2009 Sep;27(9):2301-11 PMID: 19591219
  31. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer.
    Cancer Cell. 2009 Feb 3;15(2):103-13 PMID: 19185845
  32. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis.
    Nature. 2007 Oct 4;449(7162):557-63 PMID: 17914389
  33. Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers.
    Gastroenterology. 2005 May;128(6):1567-78 PMID: 15887152
  34. Multilineage potential of adult human mesenchymal stem cells.
    Science. 1999 Apr 2;284(5411):143-7 PMID: 10102814
  35. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy.
    Blood. 2009 Apr 30;113(18):4341-51 PMID: 19139079
  36. Cancer stem cells: an old idea--a paradigm shift.
    Cancer Res. 2006 Feb 15;66(4):1883-90; discussion 1895-6 PMID: 16488983
  37. Inflammation and cancer.
    Nature. 2002 Dec 19-26;420(6917):860-7 PMID: 12490959
  38. Normal stem cells and cancer stem cells: the niche matters.
    Cancer Res. 2006 May 1;66(9):4553-7 PMID: 16651403
  39. The role of stromal stem cells in tissue regeneration and wound repair.
    Science. 2009 Jun 26;324(5935):1666-9 PMID: 19556498
  40. Gastrointestinal stem cells in development and cancer.
    J Pathol. 2009 Jan;217(2):307-17 PMID: 19031475
  41. A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis.
    Gastroenterology. 2004 Apr;126(4):955-63 PMID: 15057733
  42. Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche.
    Nature. 2009 Jan 1;457(7225):92-6 PMID: 19052546
Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2011.01.020
Published
2011-02-15
Pages
257-72
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC3060401
Subset
IM
Grants
NCI NIH HHS · R21 CA149865 · United States
NCI NIH HHS · U54 CA126513-05 · United States
NCI NIH HHS · 1U54CA126513 · United States
NCI NIH HHS · R21CA149865 · United States
NCI NIH HHS · R01 CA120979 · United States
NCI NIH HHS · R01 CA120979-05 · United States
NCI NIH HHS · R01 CA093405 · United States
NCI NIH HHS · R01CA093405 · United States
NCI NIH HHS · U54 CA126513 · United States
NCI NIH HHS · R01CA120979 · United States
NCI NIH HHS · R01 CA093405-11 · United States
Databases
GEO
GSE23548
External Links
PubMed source DOI: 10.1016/j.ccr.2011.01.020 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2