Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells
Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells
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DOI：
10.1016/j.ejca.2013.01.017
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发表时间：
2013-05-01
影响因子：
8.4
通讯作者：
O'Driscoll, Lorraine
中科院分区：
文献类型：
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作者：
O'Brien, Keith;Rani, Sweta;O'Driscoll, Lorraine
背景：三阴性乳腺癌(TNBC)占乳腺癌的15%-20%，但其死亡人数却不成比例。我们在TNBC中调查了从细胞中排出的纳米尺寸外切体的相关性。具体地说，我们比较了来自Claudin-low TNBC细胞系Hs578T及其更具侵袭性的Hs578TS(I)(8)变体的外切体以及来自TNBC患者血清的外切体与正常血清相比的效果。方法：通过过滤和超速离心从Hs578T和Hs578TS(I)(8)细胞的条件培养液(CM)和血清中分离外切体。经透射电子显微镜和免疫印迹检测证实分离成功。结果：Hs578TS(I)(8)-exosome与Hs578T-exosome相比显著增加了三种受体细胞系SKBR3、MDA-MB-231和HCC1954的增殖、迁移和侵袭能力。Hs578T(I)(8)细胞的外切体也增加了对亲本Hs578T细胞的侵袭力。Hs578T(I)(8)-与Hs578T-exosome相比，外切体增加了SKBR3、MDA-MB-231和HCC1954对失巢凋亡的敏感性，反映了Hs578TS(I)(8)细胞本身对失巢凋亡本身更敏感的事实。在血管生成和随后的血管生成方面，Hs578TS(I)(8)-exosome与Hs578T-exosome相比，显著刺激更多的内皮小管形成。最后，我们的初步翻译研究表明，与来自年龄和性别匹配的健康对照血清的外切体相比，来自TNBC患者血清的外切体显著增加了受体细胞的侵袭性。结论：这项研究支持了这样的假设，即TNBC外切体可能参与癌细胞之间的通讯，赋予次级细胞表型特征，反映其来源细胞的表型特征。(C)2013爱思唯尔有限公司。保留所有权利。
Background: Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers but is responsible for a disproportionate number of deaths. We investigated the relevance, in TNBC, of nano-sized exosomes expelled from cells. Specifically, we compared effects of exosomes derived from the claudin-low TNBC cell line Hs578T and its more invasive Hs578Ts(i)(8) variant, as well as exosomes from TNBC patient sera compared to normal sera.Methods: Exosomes were isolated from conditioned media (CM) of Hs578T and Hs578Ts(i)(8) cells and from sera by filtration and ultracentrifugation. Successful isolation was confirmed by transmission electron microscopy and immunoblotting. Subsequent analysis, of secondary/recipient cells in response to exosomes, included proliferation; motility/migration; invasion; anoikis assays and endothelial tubule formation assays.Results: Hs578Ts(i)(8)-exosomes versus Hs578T-exosomes significantly increased the proliferation, migration and invasion capacity of all three recipient cell lines evaluated i. e. SKBR3, MDA-MB-231 and HCC1954. Exosomes from Hs578Ts(i)(8) cells also conferred increased invasiveness to parent Hs578T cells. Hs578Ts(i)(8)-exosomes increased sensitivity of SKBR3, MDA-MB-231 and HCC1954 to anoikis when compared to the effects of Hs578T-exosomes reflecting the fact that Hs578Ts(i)(8) cells are themselves innately more sensitive to anoikis. In relation to vasculogenesis and subsequent angiogenesis, Hs578Ts(i)(8)-exosomes versus Hs578T-exosomes stimulated significantly more endothelial tubules formation. Finally, our pilot translational study showed that exosomes from TNBC patients' sera significantly increased recipient cells' invasion when compared to those derived from age- and gender-matched healthy control sera.Conclusion: This study supports the hypothesis that TNBC exosomes may be involved in cancer cell-to-cell communication, conferring phenotypic traits to secondary cells that reflect those of their cells of origin. (C) 2013 Elsevier Ltd. All rights reserved.