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

Guangwen Ren, Xin Zhao, Ying Wang, Xin Zhang, Xiaodong Chen, Chunliang Xu, Zeng Rong Yuan, Arthur I. Roberts, Liying Zhang, Betty Zheng, Ting Wen, Yanyan Han, Arnold B. Rabson, Jay A. Tischfield, Changshun Shao, Yufang Shi

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151 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)812-824
Number of pages13
JournalCell Stem Cell
Volume11
Issue number6
DOIs
StatePublished - Dec 7 2012

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ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Ren, G., Zhao, X., Wang, Y., Zhang, X., Chen, X., Xu, C., Yuan, Z. R., Roberts, A. I., Zhang, L., Zheng, B., Wen, T., Han, Y., Rabson, A. B., Tischfield, J. A., Shao, C., & Shi, Y. (2012). CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFα. Cell Stem Cell, 11(6), 812-824. https://doi.org/10.1016/j.stem.2012.08.013