Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment.
Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment.
复制标题
外泌体赋予促生存信号，以改变周围环境中前列腺细胞的表型。
DOI：
10.18632/oncotarget.7052
复制
发表时间：
2016-03-22
期刊：
影响因子：
--
通讯作者：
Tomlinson Guns ES
中科院分区：
文献类型：
--
作者：
Hosseini-Beheshti E;Choi W;Weiswald LB;Kharmate G;Ghaffari M;Roshan-Moniri M;Hassona MD;Chan L;Chin MY;Tai IT;Rennie PS;Fazli L;Tomlinson Guns ES
前列腺癌（PCa）是男性中最常见的癌症。目前对肿瘤相关细胞外囊泡（EV）的研究表明，外泌体在旁分泌信号通路中发挥重要作用，从而可能通过多种机制影响癌症进展。事实上，在过去的十年中，许多研究已经揭示了EV在包括癌症在内的各种病理条件进展中的作用。此外，来自PCa细胞系与良性前列腺细胞系的外泌体的蛋白质组学、脂质组学和胆固醇含量的差异证实外泌体可以是优异的生物标志物候选物。因此，作为使用LCMS的广泛蛋白质组学分析的一部分，我们先前描述了外泌体作为PCa生物标志物的潜在作用。目前的证据表明，EV吸收到局部肿瘤微环境中，这鼓励我们进一步研究这些囊泡在PCa和去势抵抗性PCa进展中所涉及的不同机制中的作用。出于本研究的目的，我们假设外泌体在局部肿瘤微环境中的细胞-细胞通信中起关键作用，在PCa进展和治疗抗性的发展期间赋予许多存活机制的激活。我们的体外结果表明，PCa衍生的外泌体在LNCaP和RWPE-1细胞中显著减少细胞凋亡，增加癌细胞增殖并诱导细胞迁移。结合我们的体外发现，我们还证明了当静脉内施用DU 145细胞衍生的外泌体时，外泌体在体内增加了肿瘤体积和血清PSA水平。这项研究表明，无论雄激素受体表型如何，来自PCa细胞的外泌体显著增强了导致PCa进展的多种机制。
Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression.