Tumor resident mesenchymal stromal cells endow naïve stromal cells with tumor-promoting properties.
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.
1] Child Health Institute of New Jersey, Robert Wood Johnson Medical School-Rutgers Biomedical and Health Sciences, New Brunswick, NJ, USA [2] Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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G
Ren
1] Department of Medical Oncology/Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, China [2] Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ, USA.
Y
Y
Liu
Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ, USA.
X
X
Zhao
Child Health Institute of New Jersey, Robert Wood Johnson Medical School-Rutgers Biomedical and Health Sciences, New Brunswick, NJ, USA.
J
J
Zhang
Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ, USA.
B
B
Zheng
Child Health Institute of New Jersey, Robert Wood Johnson Medical School-Rutgers Biomedical and Health Sciences, New Brunswick, NJ, USA.
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ZR
Yuan
Child Health Institute of New Jersey, Robert Wood Johnson Medical School-Rutgers Biomedical and Health Sciences, New Brunswick, NJ, USA.
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L
Zhang
Department of Medical Oncology/Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, China.
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X
Qu
Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ, USA.
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JA
Tischfield
1] Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ, USA [2] Ministry of Education Key Laboratory of Experimental Teratology/Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
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C
Shao
1] Child Health Institute of New Jersey, Robert Wood Johnson Medical School-Rutgers Biomedical and Health Sciences, New Brunswick, NJ, USA [2] Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Y
Y
Shi
D000818:Animals; D002471:Cell Transformation, Neoplastic; D018920:Coculture Techniques; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000502:physiology*; D059016:Tumor Microenvironment