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Metastatic state of parent cells influences the uptake and functionality of prostate cancer cell-derived extracellular vesicles.
Journal of Extracellular Vesicles ( IF 15.5 ) Pub Date : 2017-08-10 , DOI: 10.1080/20013078.2017.1354645
Elisa Lázaro-Ibáñez 1 , Maarit Neuvonen 1, 2 , Maarit Takatalo 1, 2 , Uma Thanigai Arasu 3 , Cristian Capasso 4 , Vincenzo Cerullo 4 , Johng S Rhim 5 , Kirsi Rilla 3 , Marjo Yliperttula 1 , Pia R-M Siljander 1, 2
Affiliation  

Extracellular vesicles (EVs), including microvesicles and exosomes, mediate intercellular signalling which has a profound role in cancer progression and in the development of metastasis. Internalisation of EVs can prompt functional changes in the recipient cells, the nature of which depends on the molecular composition and the cargo of the EVs. We hypothesised that the metastatic stage of cancerous parent cells would determine the uptake efficacy and the subsequent functional effects of the respective cancer cell-derived EVs. To address this question, we compared the internalisation of EVs derived from two metastatic site-derived prostate cancer cell lines (PC-3 and LNCaP), human telomerase reverse transcriptase immortalised primary malignant prostate epithelial cells (RC92a/hTERT), and a benign epithelial prostate cell line (PNT2). EVs isolated from the metastatic site-derived PC-3 and LNCaP cells were more efficiently internalised by the PC-3 and PNT2 cells compared to the EVs from the primary malignant RC92a/hTERT cells or the benign PNT2 cells, as determined by high content microscopy, confocal microscopy, and flow cytometry. EV uptake was also influenced by the phase of the cell cycle, so that an increased EV-derived fluorescence signal was observed in the cells at the G2/M phase compared to the G0/G1 or S phases. Finally, differences were also observed in the functions of the recipient cells based on the EV source. Proliferation of PNT2 cells and to a lesser extent also PC-3 cells was enhanced particularly by the EVs from the metastatic-site-derived prostate cancer cells in comparison to the EVs from the benign cells or primary cancer cells, whereas migration of PC-3 cells was enhanced by all cancerous EVs.



中文翻译:

亲代细胞的转移状态影响前列腺癌细胞衍生的细胞外囊泡的摄取和功能。

细胞外囊泡(EV),包括微囊泡和外泌体,介导细胞间信号传导,这在癌症进展和转移发展中具有重要作用。电动汽车的内在化可以促进受体细胞的功能变化,其性质取决于电动汽车的分子组成和载货。我们假设癌细胞母细胞的转移阶段将决定相应癌细胞衍生的电动汽车的吸收功效和随后的功能作用。为了解决这个问题,我们比较了源自两种转移部位的前列腺癌细胞系(PC-3和LNCaP),人类端粒酶逆转录酶永生化的原发性前列腺癌上皮细胞(RC92a / hTERT)和良性上皮细胞产生的EV的内在化前列腺细胞系(PNT2)。根据高含量显微镜检查,与原发性恶性RC92a / hTERT细胞或良性PNT2细胞的EV相比,从转移部位衍生的PC-3和LNCaP细胞分离的EV更能被PC-3和PNT2细胞内化,共聚焦显微镜和流式细胞仪。EV摄取也受细胞周期阶段的影响,因此在G处的细胞中观察到了EV衍生的荧光信号增加2 / M相与G 0 / G 1或S相相比。最后,在基于EV源的受体细胞的功能上也观察到差异。与来自良性或原发性癌细胞的EV相比,转移部位衍生的前列腺癌细胞的EV尤其增强了PNT2细胞以及PC-3细胞的增殖,所有癌性电动车均能增强细胞的活力。

更新日期:2017-08-10
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