Cancer Biology Program; Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles, CA USA.
Cell Cycle. 2013 Nov 15;12(22):3526-36. doi: 10.4161/cc.26539. Epub 2013 Sep 23.
Prostate cancer cells release atypically large extracellular vesicles (EVs), termed large oncosomes, which may play a role in the tumor microenvironment by transporting bioactive molecules across tissue spaces and through the blood stream. In this study, we applied a novel method for selective isolation of large oncosomes applicable to human platelet-poor plasma, where the presence of caveolin-1-positive large oncosomes identified patients with metastatic disease. This procedure was also used to validate results of a miRNA array performed on heterogeneous populations of EVs isolated from tumorigenic RWPE-2 prostate cells and from isogenic non-tumorigenic RWPE-1 cells. The results showed that distinct classes of miRNAs are expressed at higher levels in EVs derived from the tumorigenic cells in comparison to their non-tumorigenic counterpart. Large oncosomes enhanced migration of cancer-associated fibroblasts (CAFs), an effect that was increased by miR-1227, a miRNA abundant in large oncosomes produced by RWPE-2 cells. Our findings suggest that large oncosomes in the circulation report metastatic disease in patients with prostate cancer, and that this class of EV harbors functional molecules that may play a role in conditioning the tumor microenvironment.
前列腺癌细胞释放异常大的细胞外囊泡（EVs），称为大的肿瘤球体，它们可能通过在组织间隙和血液中运输生物活性分子在肿瘤微环境中发挥作用。在这项研究中，我们应用了一种新的方法，可选择性地分离适用于人血小板贫乏血浆的大肿瘤球体，其中存在小窝蛋白-1 阳性的大肿瘤球体可识别出患有转移性疾病的患者。该程序还用于验证从致瘤 RWPE-2 前列腺细胞和同源非致瘤 RWPE-1 细胞分离的 EV 异质群体上进行的 miRNA 阵列的结果。结果表明，与非致瘤细胞相比，源自致瘤细胞的 EV 中表达了更高水平的不同 miRNA 类别。大肿瘤球体增强了癌症相关成纤维细胞（CAFs）的迁移，这种作用通过富含 RWPE-2 细胞产生的大肿瘤球体中的 miRNA-1227 增加。我们的研究结果表明，循环中的大肿瘤球体报告了前列腺癌患者的转移性疾病，并且该 EV 类具有功能分子，可能在调节肿瘤微环境中发挥作用。
