Tumor-Derived Extracellular Vesicles Require β1 Integrins to Promote Anchorage-Independent Growth
Tumor-Derived Extracellular Vesicles Require β1 Integrins to Promote Anchorage-Independent Growth
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DOI：
10.1016/j.isci.2019.03.022
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发表时间：
2019-04-26
期刊：
影响因子：
5.8
通讯作者：
Languino, Lucia R.
中科院分区：
文献类型：
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作者：
DeRita, Rachel M.;Sayeed, Aejaz;Languino, Lucia R.
已知促进癌症进展的β 1整合素在细胞外囊泡（ev）中含量丰富。我们研究了前列腺癌（PrCa） ev是否影响锚定非依赖性生长，以及这种作用是否需要β 1整合素。具体来说，通过基于细胞系的遗传拯救和体内PrCa模型，我们发现从癌细胞或携带肿瘤的小鼠（小鼠前列腺的转基因腺癌）小鼠的血液中梯度纯化的小ev （sev）促进了PrCa细胞的锚定非依赖性生长。相比之下，从培养的含有短发夹RNA到β 1的PrCa细胞、野生型小鼠或携带β 1条件消融前列腺上皮（β 1(Pc-/-)）的TRAMP小鼠中获得的sev则没有。我们发现，来自癌细胞或TRAMP血液的sEV是功能性的，并且共同表达β 1和sEV标记物；相比之下，来自β 1(Pc-/-)/TRAMP或野生型小鼠的sEV缺乏β 1和sEV标记。我们的研究结果表明，肿瘤细胞衍生的sev需要β 1整合素来刺激非锚定生长。
The beta 1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether beta 1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to beta 1, from wild-type mice or from TRAMP mice carrying a beta 1 conditional ablation in the prostatic epithelium (beta 1(Pc-/-)), do not. We find that sEVs, from cancer cells or TRAMP blood, are functional and co-express beta 1 and sEV markers; in contrast, sEVs from beta 1(Pc-/-)/TRAMP or wild-type mice lack beta 1 and sEV markers. Our results demonstrate that beta 1 integrins in tumor-cell-derived sEVs are required for stimulation of anchorage-independent growth.