Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells
Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells
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全反式视黄酸抑制 M2 样巨噬细胞可预防骨肉瘤细胞中的癌症发生和干细胞性
DOI：
10.1038/s41401-019-0262-4
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发表时间：
2019-10-01
影响因子：
8.2
通讯作者：
He, Qiao-jun
中科院分区：
文献类型：
--
作者：
Shao, Xue-jing;Xiang, Sen-feng;He, Qiao-jun
新的证据表明，M2极化的肿瘤相关巨噬细胞（TAM）直接参与肿瘤的发生、发展和转移。然而，迄今为止，很少有研究调查了新的策略，抑制TAM，以克服骨肉瘤。在这项研究中，我们报道了M2巨噬细胞富集在患者的骨肉瘤组织中，M2极化的TAM增强了骨肉瘤细胞的癌症起始和干性，从而建立了M2极化的TAM作为阻断骨肉瘤形成的治疗靶点。全反式维甲酸（all-transretinoicacid，ATRA）在体内可通过抑制TAM的M2极化而减弱TAM诱导的骨肉瘤形成，在体外可抑制M2型巨噬细胞促进的骨肉瘤细胞的殖民地形成和成球能力。此外，M2型巨噬细胞增强了癌症干细胞（CSC）的特性，通过增加CD 117 +Stro-1+细胞的数量并伴随CSC标志物（CD 133，CXCR 4，Nanog和Oct 4）的上调来评估，这可以明显地被ATRA降低。总之，本研究的结果证明了M2极化TAM通过激活CSC在骨肉瘤起始和干性中的作用，并表明ATRA治疗是通过防止TAM的M2极化来治疗骨肉瘤的有希望的方法。
Emerging evidence indicates that M2-polarized tumor-associated macrophages (TAMs) directly participate in tumor initiation, progression and metastasis. However, to date, few studies have investigated novel strategies for inhibiting TAMs in order to overcome osteosarcoma. In this study, we reported that M2 macrophages were enriched in osteosarcoma tissues from patients, and M2-polarized TAMs enhanced cancer initiation and stemness of osteosarcoma cells, thereby establishing M2-polarized TAMs as a therapeutic target for blocking osteosarcoma formation. We also found that all-trans retinoic acid (ATRA) weakened TAM-induced osteosarcoma tumor formation by inhibiting M2 polarization of TAMs in vivo, and inhibited the colony formation, as well as sphere-formation capacity of osteosarcoma cells promoted by M2-type macrophages in vitro. Furthermore, M2-type macrophages enhanced cancer stem cells (CSCs) properties as assessed by increasing the numbers of CD117+Stro-1+ cells accompanied by the upregulation of CSC markers (CD133, CXCR4, Nanog, and Oct4), which could clearly be reduced by ATRA. Taken together, the results of this study demonstrated the role of M2-polarized TAMs in osteosarcoma initiation and stemness by activating CSCs, and indicated that ATRA treatment is a promising approach for treating osteosarcoma by preventing M2 polarization of TAMs.