CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFα.
CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFα.
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DOI：
10.1016/j.stem.2012.08.013
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发表时间：
2012-12-07
期刊：
影响因子：
23.9
通讯作者：
Shi, Yufang
中科院分区：
文献类型：
--
作者：
Ren, Guangwen;Zhao, Xin;Wang, Ying;Zhang, Xin;Chen, Xiaodong;Xu, Chunliang;Yuan, Zeng-rong;Roberts, Arthur I.;Zhang, Liying;Zheng, Betty;Wen, Ting;Han, Yanyan;Rabson, Arnold B.;Tischfield, Jay A.;Shao, Changshun;Shi, Yufang
间充质基质细胞（MSC）倾向于浸润到肿瘤中并形成肿瘤微环境的主要成分。已知这些肿瘤驻留MSC影响肿瘤生长，但其机制在很大程度上尚不清楚。我们发现从小鼠自发性淋巴瘤中分离的MSC（L-MSC）与骨髓MSC（BM-MSC）相比显著增强肿瘤生长。L-MSC有助于更多的CD 11b + Ly 6C+单核细胞，F4/80+巨噬细胞和CD 11b + Ly 6 G+中性粒细胞向肿瘤的募集。单核细胞/巨噬细胞的消耗，但不是中性粒细胞，完全取消了L-MSC的肿瘤促进。此外，L-MSC表达高水平的CCR 2配体，单核细胞/巨噬细胞积聚和L-MSC介导的肿瘤促进在CCR 2 −/−小鼠中基本上被消除。有趣的是，TNFα预处理的BM-MSCs在其趋化因子产生谱和促进淋巴瘤、黑色素瘤和乳腺癌的肿瘤发生的能力方面模仿L-MSCs。因此，我们的研究结果表明，在炎症环境中，肿瘤驻留MSC通过招募单核细胞/巨噬细胞促进肿瘤生长。
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.
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DOI：
10.1084/jem.20091046
发表时间：
2009-10-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Morikawa S;Mabuchi Y;Kubota Y;Nagai Y;Niibe K;Hiratsu E;Suzuki S;Miyauchi-Hara C;Nagoshi N;Sunabori T;Shimmura S;Miyawaki A;Nakagawa T;Suda T;Okano H;Matsuzaki Y
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Matsuzaki Y
影响因子：
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通讯作者：
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影响因子：
15.3
作者：
Davidson, W F;Giese, T;Fredrickson, T N
通讯作者：
Fredrickson, T N
影响因子：
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作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
20.3
作者：
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通讯作者：
Ward, JM