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Extracellular vesicles from MDA-MB-231 breast cancer cells stimulated with insulin-like growth factor 1 mediate an epithelial–mesenchymal transition process in MCF10A mammary epithelial cells
Journal of Cell Communication and Signaling ( IF 3.6 ) Pub Date : 2021-07-26 , DOI: 10.1007/s12079-021-00638-y
Elizabeth Leal-Orta 1 , Javier Ramirez-Ricardo 1 , Alejandra Garcia-Hernandez 1 , Pedro Cortes-Reynosa 1 , Eduardo Perez Salazar 1
Affiliation  

Insulin-like growth factor-1 (IGF-1) plays an important role in function and development of the mammary gland. However, high levels of IGF-1 has been associated with an increased risk of breast cancer development. Epithelial–mesenchymal transition (EMT) is a process where epithelial cells lose their epithelial characteristics and acquire a mesenchymal phenotype, which is considered one of the most important mechanisms in cancer initiation and promotion of metastasis. Extracellular vesicles (EVs) are released into the extracellular space by different cell types, which mediate intercellular communication and play an important role in different physiological and pathological processes, such as cancer. In this study, we demonstrate that EVs from MDA-MB-231 breast cancer cells stimulated with IGF-1 (IGF-1 EVs) decrease the levels of E-cadherin, increase the expression of vimentin and N-cadherin and stimulate the secretion of metalloproteinase-9 in mammary non-tumorigenic epithelial cells MCF10A. IGF-1 EVs also induce the expression of Snail1, Twist1 and Sip1, which are transcription factors involved in EMT. Moreover, IGF-1 EVs induce activation of ERK1/2, Akt1 and Akt2, migration and invasion. In summary, we demonstrate, for the first time, that IGF-1 EVs induce an EMT process in mammary non-tumorigenic epithelial cells MCF10A.



中文翻译:

胰岛素样生长因子 1 刺激的 MDA-MB-231 乳腺癌细胞的细胞外囊泡介导 MCF10A 乳腺上皮细胞的上皮-间质转化过程

胰岛素样生长因子 1 (IGF-1) 在乳腺的功能和发育中起着重要作用。然而,高水平的 IGF-1 与乳腺癌发展的风险增加有关。上皮-间质转化(EMT)是上皮细胞失去其上皮特征并获得间充质表型的过程,这被认为是癌症起始和促进转移的最重要机制之一。细胞外囊泡(EVs)由不同类型的细胞释放到细胞外空间,介导细胞间通讯并在不同的生理和病理过程中发挥重要作用,例如癌症。在这项研究中,我们证明来自用 IGF-1 (IGF-1 EV) 刺激的 MDA-MB-231 乳腺癌细胞的 EV 降低了 E-钙粘蛋白的水平,增加波形蛋白和 N-钙粘蛋白的表达并刺激乳腺非致瘤性上皮细胞 MCF10A 中金属蛋白酶 9 的分泌。IGF-1 EV 还诱导 Snail1、Twist1 和 Sip1 的表达,它们是参与 EMT 的转录因子。此外,IGF-1 EV 可诱导 ERK1/2、Akt1 和 Akt2 的激活、迁移和侵袭。总之,我们首次证明 IGF-1 EV 在乳腺非致瘤性上皮细胞 MCF10A 中诱导 EMT 过程。

更新日期:2021-07-26
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