Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility.
Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility.
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DOI：
10.1016/j.jbiomech.2015.10.003
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发表时间：
2016-05-24
影响因子：
2.4
通讯作者：
Reinhart-King CA
中科院分区：
文献类型：
--
作者：
Bordeleau F;Chan B;Antonyak MA;Lampi MC;Cerione RA;Reinhart-King CA
在肿瘤进展过程中，癌细胞与局部微环境中的非恶性细胞相互作用和通讯。来自人类癌细胞的微泡（MV）在介导这种通讯中发挥着重要作用。癌症进展的另一个关键方面涉及广泛的 ECM 重塑，它发生在原发部位和转移部位。肿瘤微环境内的ECM重塑和重组通常归因于成纤维细胞。在这里，我们使用 MCF10a 细胞（一种表现出非恶性上皮表型的良好表征的乳腺上皮细胞系）和侵袭性 MDA-MB-231 癌细胞脱落的 MV，证明非恶性上皮细胞在用癌细胞来源的 MV 处理后可以参与 3D 胶原基质的 ECM 重组。此外，MV 在 3D 培养条件下会引发上皮细胞的多种变化。此外，我们发现这种 ECM 重组与 MV 治疗后细胞牵引力的增加、肌动球蛋白收缩力的提高和 FAK 活性的提高有关。总体而言，我们的研究结果表明，源自肿瘤细胞的 MV 可以通过增强非恶性上皮细胞的收缩性，促进肿瘤微环境中发生的 ECM 重组。
During tumor progression, cancer cells interact and communicate with non-malignant cells within their local microenvironment. Microvesicles (MV) derived from human cancer cells play an important role in mediating this communication. Another critical aspect of cancer progression involves widespread ECM remodeling, which occur both at the primary and metastatic sites. ECM remodeling and reorganization within the tumor microenvironment is generally attributed to fibroblasts. Here, using MCF10a cells, a well-characterized breast epithelial cell line that exhibits a non-malignant epithelial phenotype, and MVs shed by aggressive MDA-MB-231 carcinoma cells, we show that non-malignant epithelial cells can participate in ECM reorganization of 3D collagen matrices following their treatment with cancer cell-derived MVs. In addition, MVs trigger several changes in epithelial cells under 3D culture conditions. Furthermore, we show that this ECM reorganization is associated with an increase in cellular traction force following MV treatment, higher acto-myosin contractility, and higher FAK activity. Overall, our findings suggests that MVs derived from tumor cells can contribute to ECM reorganization occurring within the tumor microenvironment by enhancing the contractility of non-malignant epithelial cells.