Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer.
Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer.
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ETS1上调肿瘤源性外泌体中的层粘连蛋白重编程网膜巨噬细胞以促进卵巢癌的网膜转移
DOI：
10.1038/s41419-022-05472-7
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发表时间：
2022-12-07
影响因子：
9
通讯作者：
Zhao S
中科院分区：
文献类型：
--
作者：
Li H;Zeng C;Shu C;Cao Y;Shao W;Zhang M;Cao H;Zhao S
肿瘤来源的外泌体参与卵巢癌的肿瘤转移性定植，通过诱导的自适应反应在肿瘤微环境中，细胞 - 细胞在原发性肿瘤细胞和远处的微观环境之间通过外泌体进行通信在这里不了解。与对照外泌体相比，外泌体可以通过整合素和层粘连蛋白相互作用来吸收外泌体。以及在巨噬细胞中产生更多的CXCL5和CCL2，通过整合蛋白αVβ5/AKT/SP1信号在体内实验。 Exos通过介导巨噬细胞的肿瘤促进作用来促进卵巢癌的肿瘤转移，而巨噬细胞可以通过整联蛋白ανβ5抑制剂cilengitide中和，这些结果表明ETS1可以驱动卵巢癌细胞释放出较高的腹膜胶质素水平的外s-腹蛋白素水平的卵巢癌细胞通过整联蛋白αVβ5/AKT/SP1信号通路和整合素ανβ5抑制剂cilengitide通过整合蛋白αVβ5/Akt/sp1信号通路的介导的促巨噬细胞介导的促逆转录效应可以抑制由肿瘤衍生的外泌体驱动的卵巢癌的骨转移。
Tumor-derived exosomes participate in omental metastatic colonization of ovarian cancer by inducing an adaptive response in the tumor microenvironment. However, cell–cell communication via exosomes between primary tumor cells and the microenvironment of distant omentum and the mechanism of pre-metastatic niche formation are poorly understood. Here, we demonstrated that ETS1-overexpressing ovarian cancer cells secreted larger exosomes with higher laminin levels. In addition, ovarian cancer exosomes could be taken up by omental macrophages through integrin and laminin interaction. Compared with control exosomes, exosomes derived from ETS1-overexpressing ovarian cancer cells (LV-ETS1 Exos) stimulated the polarization of more macrophages toward the M2 phenotype (CD163 marker), as well as the production of more CXCL5 and CCL2 in macrophages, via integrin αvβ5/AKT/Sp1 signaling. In vivo experiments showed that LV-ETS1 Exos promoted omental metastasis of ovarian cancer by mediating the tumor-promoting effect of macrophages, which could be neutralized by integrin ανβ5 inhibitor cilengitide. These results indicated that ETS1 could drive ovarian cancer cells to release exosomes with higher laminin levels, thereby accelerating the exosome-mediated pro-metastatic effects of omental macrophages via the integrin αvβ5/AKT/Sp1 signaling pathway, and the integrin ανβ5 inhibitor cilengitide could inhibit omental metastasis of ovarian cancer driven by tumor-derived exosomes.
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