Tumor resident mesenchymal stromal cells endow naive stromal cells with tumor-promoting properties
Tumor resident mesenchymal stromal cells endow naive stromal cells with tumor-promoting properties
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DOI：
10.1038/onc.2013.387
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发表时间：
2014-07-24
期刊：
影响因子：
8
通讯作者：
Shi, Y.
中科院分区：
文献类型：
--
作者：
Ren, G.;Liu, Y.;Shi, Y.
骨髓间充质干细胞/基质细胞（BM-MSCs）可以浸润到肿瘤中，随后在肿瘤微环境中进化为肿瘤驻留的MSCs。在这项研究中，我们使用小鼠淋巴瘤模型表明，淋巴瘤驻留 MSC (L-MSC) 能够赋予初始共培养的 BM-MSC 促肿瘤特性。细胞因子和趋化因子的检查表明，暴露于 L-MSC 后，BM-MSC 获得了与 L-MSC 相似的表达谱。在体内，由L-MSC（BM-L-MSC）培养的BM-MSC具有极大增强的促进淋巴瘤生长的能力。与 BM-L-MSC 中 CCL-2 表达升高一致，BM-L-MSC 的促肿瘤作用很大程度上取决于 CCR2 介导的巨噬细胞向肿瘤部位的募集。我们进一步表明，促肿瘤作用的传递部分是由可溶性因子介导的。因此，我们的研究结果揭示了维持肿瘤微环境的一种新的强化机制。
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 naive 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.