title: CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFα.
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.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Ren
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.forename: Chunliang
authors.initials: C
authors.lastname: Xu
authors.forename: Zeng-rong
authors.initials: ZR
authors.lastname: Yuan
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Roberts
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.forename: Betty
authors.initials: B
authors.lastname: Zheng
authors.forename: Ting
authors.initials: T
authors.lastname: Wen
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Han
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Rabson
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D002450:Cell Communication; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000473:pathology*; D008223:Lymphoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000473:pathology; D054390:Receptors, CCR2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D054390:Receptors, CCR2; D014409:Tumor Necrosis Factor-alpha