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

Cancer Cell. 2011 Feb 15;19(2):257-72. doi: 10.1016/j.ccr.2011.01.020.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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
  • Neoplasms, Experimental / pathology*
  • Receptors, CXCR4 / metabolism
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation


  • Actins
  • CXCR4 protein, mouse
  • Grem1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Receptors, CXCR4
  • Transforming Growth Factor beta
  • alpha-smooth muscle actin, mouse

Associated data

  • GEO/GSE23548