Jiangsu Key Laboratory of Clinical Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Int J Oncol. 2019 May;54(5):1843-1852. doi: 10.3892/ijo.2019.4747. Epub 2019 Mar 13.
Mesenchymal stem cells (MSCs) have been demonstrated to be involved in tumor progression and the modulation of the tumor microenvironment, partly through their secretome. Extracellular vesicles (EVs) are membranous nanovesicles secreted by multiple types of cells and have been demonstrated to mediate intercellular communication in both physiological and pathological conditions. However, numerous questions still remain regarding the underlying mechanisms and functional consequences of these interactions. The purpose of this study was to investigate the effects of human umbilical cord mesenchymal stem cell‑derived EVs (hUC‑MSC‑EVs) on the proliferation, migration and invasion of human breast cancer cells. We successfully generated and identified hUC‑MSCs and hUC‑MSC‑EVs which were used in this study. The results revealed that treatment of the MDA‑MB‑231 and MCF‑7 human breast cancer cells with medium containing hUC‑MSC‑EVs significantly enhanced the proliferation, migration and invasion of the cells in vitro. Treatment of the cells with medium containing hUC‑MSC‑EVs also reduced E‑cadherin expression and increased N‑cadherin expression, thus promoting the epithelial‑mesenchymal transition (EMT) of the breast cancer cells. Treatment of the breast cancer cells with extracellular signal‑regulated kinase (ERK) inhibitor prior to the interaction with hUC‑MSC‑EVs significantly reversed the enhanced proliferation, migration and invasion, as well as the EMT of the breast cancer cells induced by the hUC‑MSC‑EVs. On the whole, these data indicate that hUC‑MSC‑EVs promote the invasive and migratory potential of breast cancer cells through the induction of EMT via the ERK pathway, leading to malignant tumor progression and metastasis. Taken together, the findings of this study suggest that targeting pathways to reverse EMT may lead to the development of novel therapeutic approaches with which to combat breast cancer.
间充质干细胞(MSCs)已被证明参与肿瘤的进展和肿瘤微环境的调节,部分是通过其分泌组。细胞外囊泡(EVs)是多种细胞分泌的膜性纳米囊泡,已被证明在生理和病理条件下介导细胞间通讯。然而,关于这些相互作用的潜在机制和功能后果仍有许多问题。本研究旨在探讨人脐带间充质干细胞衍生的细胞外囊泡(hUC-MSC-EVs)对人乳腺癌细胞增殖、迁移和侵袭的影响。我们成功地生成并鉴定了 hUC-MSCs 和 hUC-MSC-EVs,这些细胞用于本研究。结果表明,用含有 hUC-MSC-EVs 的培养基处理 MDA-MB-231 和 MCF-7 人乳腺癌细胞,显著增强了细胞在体外的增殖、迁移和侵袭能力。用含有 hUC-MSC-EVs 的培养基处理细胞还降低了 E-钙黏蛋白的表达,增加了 N-钙黏蛋白的表达,从而促进了乳腺癌细胞的上皮-间充质转化(EMT)。在与 hUC-MSC-EVs 相互作用之前,用细胞外信号调节激酶(ERK)抑制剂处理乳腺癌细胞,可显著逆转 hUC-MSC-EVs 诱导的乳腺癌细胞增殖、迁移和侵袭增强以及 EMT。总的来说,这些数据表明,hUC-MSC-EVs 通过 ERK 通路诱导 EMT 促进乳腺癌细胞的侵袭和迁移潜能,导致恶性肿瘤的进展和转移。综上所述,本研究的结果表明,靶向逆转 EMT 的途径可能导致开发新的治疗方法来对抗乳腺癌。