CCR2-Dependent Recruitment of Macrophages by Tumor-Educated Mesenchymal Stromal Cells Promotes Tumor Development and Is Mimicked by TNF
Ces deux études mettent en évidence des mécanismes impliquant les cellules stromales mésenchymateuses dans la croissance tumorale
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, TNF
α
-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.
º Tumor-resident MSCs promote tumor growth more potently than normal tissue MSCs
º Tumor-resident MSCs recruit monocytes/macrophages that are crucial for tumor growth
º Tumor-resident MSCs produce abundant CCR2 ligands for monocyte/macrophage trafficking
º TNF
α
-pretreated BM-MSCs enhance tumor progression similarly to tumor-derived MSCs
Mesenchymal stromal cells infiltrating tumors are educated by local TNF-alpha to produce CCR2 ligands. As a result, monocytes/macrophages are recruited to the tumor mass, which in turn promotes tumor growth.
Cell stem cell , résumé, 2011