Retinoic Acid Inhibits Tumor-Associated Mesenchymal Stromal Cell Transformation in Melanoma.

Retinoic Acid Inhibits Tumor-Associated Mesenchymal Stromal Cell Transformation in Melanoma.
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DOI:
10.3389/fcell.2021.658757
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发表时间:
2021
影响因子:
5.5
通讯作者:
Zhao M
Zhao M
中科院分区:
生物学2区
文献类型:
--
作者:
Lou Q;Zhao M;Xu Q;Xie S;Liang Y;Chen J;Yuan L;Wang L;Jiang L;Mou L;Lin D;Zhao M

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骨髓间充质干/基质细胞(BMSCs)可以在肿瘤微环境中转化为肿瘤相关MSCs(TA-MSCs)以促进肿瘤进展。然而,其潜在的机制和治疗策略仍不清楚。在这里,我们探讨了白细胞介素17(IL-17)与IFNγ协同作用将BMSCs转化为TA-MSCs,TA-MSCs通过招募小鼠黑色素瘤中的巨噬细胞/单核细胞和髓源性抑制细胞(MDSC)来促进肿瘤进展。IL-17和IFNγ转化的TA-MSCs具有高水平的由活化的NF-κB信号通路介导的髓细胞募集趋化因子(CCL 2、CCL 5、CCL 7和CCL 20)的表达。此外,视黄酸抑制NF-κB信号传导,降低趋化因子表达,并通过抑制肿瘤微环境中巨噬细胞/单核细胞和MDSC的募集来抑制转化的TA-MSC的促肿瘤功能。总之,我们的研究结果表明,IL-17与IFNγ协同诱导TA-MSC转化,其可以被RA靶向用于黑色素瘤治疗。
Bone marrow mesenchymal stem/stromal cells (BMSCs) can be transformed into tumor-associated MSCs (TA-MSCs) within the tumor microenvironment to facilitate tumor progression. However, the underline mechanism and potential therapeutic strategy remain unclear. Here, we explored that interleukin 17 (IL-17) cooperating with IFNγ transforms BMSCs into TA-MSCs, which promotes tumor progression by recruiting macrophages/monocytes and myeloid-derived suppressor cells (MDSCs) in murine melanoma. IL-17 and IFNγ transformed TA-MSCs have high expression levels of myelocyte-recruiting chemokines (CCL2, CCL5, CCL7, and CCL20) mediated by activated NF-κB signaling pathway. Furthermore, retinoic acid inhibits NF-κB signaling, decreases chemokine expression, and suppresses the tumor-promoting function of transformed TA-MSCs by prohibiting the recruitment of macrophages/monocytes and MDSCs in the tumor microenvironment. Overall, our findings demonstrate that IL-17 collaborating with IFNγ to induce TA-MSC transformation, which can be targeted by RA for melanoma treatment.
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