CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFα

Cell Stem Cell. 2012 Dec 7;11(6):812-24. doi: 10.1016/j.stem.2012.08.013. Epub 2012 Nov 15.


Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major component of the tumor microenvironment. These tumor-resident MSCs are known to affect tumor growth, but the mechanisms are largely unknown. We found that MSCs isolated from spontaneous lymphomas in mouse (L-MSCs) strikingly enhanced tumor growth in comparison to bone marrow MSCs (BM-MSCs). L-MSCs contributed to greater recruitment of CD11b(+)Ly6C(+) monocytes, F4/80(+) macrophages, and CD11b(+)Ly6G(+) neutrophils to the tumor. Depletion of monocytes/macrophages, but not neutrophils, completely abolished tumor promotion of L-MSCs. Furthermore, L-MSCs expressed high levels of CCR2 ligands, and monocyte/macrophage accumulation and L-MSC-mediated tumor promotion were largely abolished in CCR2(-/-) mice. Intriguingly, TNFα-pretreated BM-MSCs mimicked L-MSCs in their chemokine production profile and ability to promote tumorigenesis of lymphoma, melanoma, and breast carcinoma. Therefore, our findings demonstrate that, in an inflammatory environment, tumor-resident MSCs promote tumor growth by recruiting monocytes/macrophages.

Publication types

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

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Cell Communication
  • Cell Movement / immunology
  • Cell Proliferation
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / pathology*
  • Lymphoma / immunology*
  • Lymphoma / metabolism
  • Lymphoma / pathology*
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / pathology
  • Neoplasm Transplantation
  • Neutrophils / pathology
  • Receptors, CCR2 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Receptors, CCR2
  • Tumor Necrosis Factor-alpha