title: Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities.
abstract: Mesenchymal stromal cells (MSCs) are a major component of the tumour microenvironment. A plethora of elegant studies focusing on tumour-derived MSCs have shown that they, unlike normal MSCs in other tissue, exhibit a strong ability to promote tumour progression. However, the mechanisms underlying the conversion of normal MSCs into tumour-associated MSCs are unknown. We report here a critical role of tumour cell-derived exosomes in endowing bone marrow-derived MSCs (BM-MSCs) with a tumour-favourable phenotype. Tumour cell-derived exosomes affected neither the growth factor production nor the immunosuppressive property of MSCs; rather, they endowed MSCs with a strong ability to promote macrophage infiltration into B16-F0 melanoma or EL-4 lymphoma. Ablation of macrophages by clodronate liposome administration reversed the tumour-promoting effect of MSCs educated by tumour cell-derived exosomes (TE-MSCs) on the tumour growth. By comparing the chemokine profile of BM-MSCs with that of TE-MSCs, we found that TE-MSCs produced a large amount of CCR2 ligands, CCL2 and CCL7, which are responsible for macrophage recruitment. CCR2-specific inhibitor was found to block the tumour-promoting effect of TE-MSCs. Thus, our investigations demonstrated that tumour cell-derived exosomes confer BM-MSCs the ability to enhance tumour growth. Therefore, we uncovered a novel mechanism underlying the conversion of normal MSCs to tumour-associated MSCs.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences and Shanghai Jiao Tong University of Medicine, Shanghai, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Lin
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences and Shanghai Jiao Tong University of Medicine, Shanghai, China.
authors.forename: L M
authors.initials: LM
authors.lastname: Du
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences and Shanghai Jiao Tong University of Medicine, Shanghai, China.
authors.forename: K
authors.initials: K
authors.lastname: Cao
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences and Shanghai Jiao Tong University of Medicine, Shanghai, China.
authors.forename: Y
authors.identifier: 0000-0001-5602-9871
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences and Shanghai Jiao Tong University of Medicine, Shanghai, China.
authors.forename: P F
authors.initials: PF
authors.lastname: Yu
authors.affiliation: The First Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, 199 Renai Road, Suzhou, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences and Shanghai Jiao Tong University of Medicine, Shanghai, China.
authors.forename: F Y
authors.initials: FY
authors.lastname: Li
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences and Shanghai Jiao Tong University of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences and Shanghai Jiao Tong University of Medicine, Shanghai, China.|The First Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, 199 Renai Road, Suzhou, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Shi
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D055252:Cell-Derived Microparticles; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism*; D054390:Receptors, CCR2 / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D054390:Receptors, CCR2