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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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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