Cell Death & Disease ( IF 8.1 ) Pub Date : 2023-08-04 , DOI: 10.1038/s41419-023-06007-4
Jun-Qi Luo 1 , Tao-Wei Yang 1 , Jun Wu 1 , Hou-Hua Lai 1 , Li-Bin Zou 1 , Wen-Bin Chen 1 , Xu-Min Zhou 1 , Dao-Jun Lv 2 , Sheng-Ren Cen 1 , Zi-Ning Long 1 , Yi-You Mao 1 , Peng-Xiang Zheng 1 , Xiao-Hong Su 1 , Zhi-Yong Xian 3 , Fang-Peng Shu 4 , Xiang-Ming Mao 1
|
Tumor-derived exosomes and their contents promote cancer metastasis. Phosphoglycerate mutase 1 (PGAM1) is involved in various cancer-related processes. Nevertheless, the underlying mechanism of exosomal PGAM1 in prostate cancer (PCa) metastasis remains unclear. In this study, we performed in vitro and in vivo to determine the functions of exosomal PGAM1 in the angiogenesis of patients with metastatic PCa. We performed Glutathione-S-transferase pulldown, co-immunoprecipitation, western blotting and gelatin degradation assays to determine the pathway mediating the effect of exosomal PGAM1 in PCa. Our results revealed a significant increase in exosomal PGAM1 levels in the plasma of patients with metastatic PCa compared to patients with non-metastatic PCa. Furthermore, PGAM1 was a key factor initiating PCa cell metastasis by promoting invadopodia formation and could be conveyed by exosomes from PCa cells to human umbilical vein endothelial cells (HUVECs). In addition, exosomal PGAM1 could bind to γ-actin (ACTG1), which promotes podosome formation and neovascular sprouting in HUVECs. In vivo results revealed exosomal PGAM1 enhanced lung metastasis in nude mice injected with PCa cells via the tail vein. In summary, exosomal PGAM1 promotes angiogenesis and could be used as a liquid biopsy marker for PCa metastasis.
中文翻译:

外泌体PGAM1通过与ACTG1相互作用促进前列腺癌血管生成和转移
肿瘤来源的外泌体及其内容物促进癌症转移。磷酸甘油酸变位酶 1 (PGAM1) 参与多种癌症相关过程。然而,外泌体 PGAM1 在前列腺癌(PCa)转移中的潜在机制仍不清楚。在这项研究中,我们在体外和体内进行了确定外泌体 PGAM1 在转移性 PCa 患者血管生成中的功能。我们进行了谷胱甘肽-S-转移酶下拉、免疫共沉淀、蛋白质印迹和明胶降解测定,以确定介导外泌体 PGAM1 在 PCa 中的作用的途径。我们的结果显示,与非转移性前列腺癌患者相比,转移性前列腺癌患者血浆中外泌体 PGAM1 水平显着增加。此外,PGAM1是通过促进侵袭伪足形成启动PCa细胞转移的关键因素,并且可以通过外泌体从PCa细胞转运至人脐静脉内皮细胞(HUVEC)。此外,外泌体PGAM1可以与γ-肌动蛋白(ACTG1)结合,促进HUVEC中足体的形成和新血管的萌芽。体内结果显示,通过尾静脉注射 PCa 细胞的裸鼠中,外泌体 PGAM1 增强了肺转移。总之,外泌体 PGAM1 促进血管生成,可用作 PCa 转移的液体活检标志物。