Cancer stem-like cells derived from chemoresistant tumors have a unique capacity to prime tumorigenic myeloid cells.
Cancer stem-like cells derived from chemoresistant tumors have a unique capacity to prime tumorigenic myeloid cells.
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DOI：
10.1158/0008-5472.can-13-2169
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发表时间：
2014-05
期刊：
影响因子：
11.2
通讯作者：
T. Yamashina;Muhammad Baghdadi;A. Yoneda;I. Kinoshita;S. Suzu;H. Dosaka-akita;M. Jinushi
中科院分区：
文献类型：
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作者：
T. Yamashina;Muhammad Baghdadi;A. Yoneda;I. Kinoshita;S. Suzu;H. Dosaka-akita;M. Jinushi
对抗癌疗法的抗性极大地影响肿瘤细胞的表型和功能特性，但化学抗性如何有助于癌症干细胞样细胞的致瘤活性仍不清楚。在这项研究中，我们发现来自化疗耐药肿瘤（CSC-R）的癌症干细胞样细胞的一个特征是能够产生多种促炎细胞因子，并从CD 14（+）单核细胞产生M2样免疫调节髓样细胞。此外，我们确定了IFN调节的转录因子IRF 5作为CSC-R特异性因子，其对于促进M-CSF产生和产生致瘤性髓样细胞至关重要。重要的是，用IRF 5（+）CSC-R致敏的骨髓细胞促进大块肿瘤的致瘤性和干细胞活性。重要的是，肿瘤细胞中IRF 5/M-CSF通路的激活与非小细胞肺癌患者中肿瘤相关CSF 1受体（+）M2巨噬细胞的数量相关。总的来说，我们的研究结果显示了化学抗性如何影响CSC在其生态位微环境中的特性。
Resistance to anticancer therapeutics greatly affects the phenotypic and functional properties of tumor cells, but how chemoresistance contributes to the tumorigenic activities of cancer stem-like cells remains unclear. In this study, we found that a characteristic of cancer stem-like cells from chemoresistant tumors (CSC-R) is the ability to produce a variety of proinflammatory cytokines and to generate M2-like immunoregulatory myeloid cells from CD14(+) monocytes. Furthermore, we identified the IFN-regulated transcription factor IRF5 as a CSC-R-specific factor critical for promoting M-CSF production and generating tumorigenic myeloid cells. Importantly, myeloid cells primed with IRF5(+) CSC-R facilitate the tumorigenic and stem cell activities of bulk tumors. Importantly, the activation of IRF5/M-CSF pathways in tumor cells were correlated with the number of tumor-associated CSF1 receptor(+) M2 macrophages in patients with non-small lung cancer. Collectively, our findings show how chemoresistance affects the properties of CSCs in their niche microenvironments.