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Tumor resident mesenchymal stromal cells endow naïve stromal cells with tumor-promoting properties

Oncogene volume 33, pages 4016–4020 (2014)Cite this article

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Abstract

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) can infiltrate into tumors and subsequently evolve into tumor resident MSCs in tumor microenvironment. In this study, using a mouse lymphoma model, we showed that the lymphoma resident MSCs (L-MSCs) are able to confer tumor-promoting property to the naïve cocultured BM-MSCs. Examination of cytokines and chemokines showed that post exposure to L-MSCs, BM-MSCs acquired an expression profile that is similar to that in L-MSCs. In vivo, BM-MSCs educated by L-MSCs (BM-L-MSCs) possess a greatly enhanced ability in promoting lymphoma growth. Consistent with an elevated CCL-2 expression in BM-L-MSCs, the tumor-promoting effect of BM-L-MSCs largely depends on CCR2-mediated macrophage recruitment to tumor sites. We further showed that the transmission of tumor-promoting effect is partially mediated by soluble factors. Our findings thus revealed a novel reinforcing mechanism in the maintenance of tumor microenvironment.

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Abbreviations

BM-MSCs:

bone marrow-derived mesenchymal stromal cells

L-MSCs:

lymphoma-derived mesenchymal stromal cells

BM-L-MSCs:

BM-MSCs after coculture with L-MSCs

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Acknowledgements

This work was supported by grants from National Institutes of Health of the United States of America (GM866889, DE014913, DE019932 and ES005022), Ministry of Science and Technology of China (2010CB945600 and 2011DFA30630) and a grant from the Human Genetics Institute of New Jersey. We would also like to thank the Robert Wood Johnson Foundation (Grant 67038) for their support of the Child Health Institute of New Jersey.

Author contributions

GR and YL designed the research, collected data, analyzed and interpreted data and drafted the manuscript. XZ, JZ, BZ, YZ, LZ and XQ collected data, analyzed and interpreted data. JT, CS and YS designed the research, analyzed and interpreted data, and drafted the manuscript.

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Author notes

  1. G Ren

    Present address: 7Current address: Department of Molecular Biology, Washington Road, Princeton University, Princeton, NJ 08544, USA,

  2. G Ren and Y Liu: These authors contributed equally.

Authors and Affiliations

  1. Child Health Institute of New Jersey, Robert Wood Johnson Medical School-Rutgers Biomedical and Health Sciences, New Brunswick, NJ, USA

    G Ren, J Zhang, Z-R Yuan, L Zhang & Y Shi

  2. Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China

    G Ren & Y Shi

  3. Department of Medical Oncology/Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, China

    Y Liu & X Qu

  4. Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ, USA

    Y Liu, X Zhao, B Zheng, J A Tischfield & C Shao

  5. Ministry of Education Key Laboratory of Experimental Teratology/Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong, China

    C Shao

Authors
  1. G Ren
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Corresponding authors

Correspondence to C Shao or Y Shi.

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Supplementary Information accompanies this paper on the Oncogene website

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Ren, G., Liu, Y., Zhao, X. et al. Tumor resident mesenchymal stromal cells endow naïve stromal cells with tumor-promoting properties. Oncogene 33, 4016–4020 (2014). https://doi.org/10.1038/onc.2013.387

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  • DOI: https://doi.org/10.1038/onc.2013.387

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