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Linoleic acid induces secretion of extracellular vesicles from MDA-MB-231 breast cancer cells that mediate cellular processes involved with angiogenesis in HUVECs
ProstaglandIns & Other Lipid Mediators ( IF 2.9 ) Pub Date : 2020-11-22 , DOI: 10.1016/j.prostaglandins.2020.106519
Alejandra Garcia-Hernandez 1 , Elizabeth Leal-Orta 1 , Javier Ramirez-Ricardo 1 , Pedro Cortes-Reynosa 1 , Rocio Thompson-Bonilla 2 , Eduardo Perez Salazar 1
Affiliation  

Extracellular vesicles (EVs) are vesicles secreted by normal and malignant cells that are implicated in tumor progression. Linoleic acid (LA) is an essential polyunsaturated fatty acid that induces migration, invasion and an increase in phospholipase D activity in breast cancer cells. In this study, we determined whether stimulation of MDA-MB-231 breast cancer cells with LA induces the secretion of EVs, which can mediate cell processes related with angiogenesis in human umbilical vein endothelial cells (HUVECs). Our findings demonstrate that treatment of MDA-MB-231 cells with 90 μM LA for 48 h induce an increase in the number of EVs released. Moreover, EVs from MDA-MB-231 stimulated with 90 μM LA induce FAK and Src activation and migration via FAK and Src activity, whereas the secretion of these EVs is through FFAR1 and FFAR4 activation in HUVECs. The EVs from MDA-MB-231 cells treated with LA also increase proliferation, invasion, MMP-9 secretion, an increase of MMP-2 secretion and formation of new tubules in HUVECs. In summary, we demonstrate, for the first time, that treatment with LA induces the release of EVs from MDA-MB-231 cells that induce cellular processes involved with angiogenesis in HUVECs.



中文翻译:

亚油酸诱导 MDA-MB-231 乳腺癌细胞分泌细胞外囊泡,后者介导与 HUVEC 血管生成有关的细胞过程

细胞外囊泡 (EV) 是由与肿瘤进展有关的正常和恶性细胞分泌的囊泡。亚油酸 (LA) 是一种必需的多不饱和脂肪酸,可诱导乳腺癌细胞的迁移、侵袭和磷脂酶 D 活性的增加。在这项研究中,我们确定了用 LA 刺激 MDA-MB-231 乳腺癌细胞是否会诱导 EVs 的分泌,EVs 可以介导与人脐静脉内皮细胞 (HUVECs) 血管生成相关的细胞过程。我们的研究结果表明,用 90 μM LA 处理 MDA-MB-231 细胞 48 小时会导致释放的 EV 数量增加。此外,来自用 90 μM LA 刺激的 MDA-MB-231 的 EV 通过 FAK 和 Src 活性诱导 FAK 和 Src 激活和迁移,而这些 EV 的分泌是通过 HUVEC 中的 FFAR1 和 FFAR4 激活。来自用 LA 处理的 MDA-MB-231 细胞的 EV 也增加增殖、侵袭、MMP-9 分泌、MMP-2 分泌增加和 HUVEC 中新小管的形成。总之,我们首次证明,用 LA 治疗会诱导 MDA-MB-231 细胞释放 EV,这些细胞会诱导参与 HUVEC 血管生成的细胞过程。

更新日期:2020-12-05
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