Abstract：
Exosome-mediated epithelial mesenchymal transition (EMT) is key to cancer metastasis. c-Src is involved in the secretion of exosomes and initiation of EMT. Effects of exosomes from metastatic non-small cell lung carcinoma (NSCLC) cells on the EMT process in primary NSCLC cells were assessed. Levels of c-Src in NSCLC tissues were detected and the influence of exosomes from metastatic NSCLC cells on the exosome secretion and EMT process in primary NSCLC cells was assessed. The expression of c-Src was modulated, and the influence on the secretion of exosomes and EMT initiation was evaluated. The level of c-Src was higher in NSCLC specimen and NSCLC cells with promoted EMT process. The suppression of c-Src inhibited secretion of exosomes. Exosomes from metastatic NSCLC cells enhanced migration and invasion abilities of primary NSCLC cells, which had identical effects to c-Src overexpression. The suppression of c-Src inhibited growth and metastasis of solid tumors as well as secretion of exosomes, while the injection of exosomes with c-Src overexpression promoted lung metastasis. TGF-β1 restored the invasion and migration abilities even with c-Src knockdown. The exosomes from metastatic NSCLC cells with high c-Src expression of can increase c-Src level in primary NSCLC cells, contributing to the promoted EMT process through TGF-β1 pathway.
摘要：
外泌体介导的上皮间质转化（EMT）是癌症转移的关键。c-Src参与外泌体的分泌和EMT的启动。评估了来自转移性非小细胞肺癌（NSCLC）细胞的外泌体对原代NSCLC细胞中EMT过程的影响。检测NSCLC组织中的c-Src水平,并评估来自转移性NSCLC细胞的外泌体对原代NSCLC细胞中的外泌体分泌和EMT过程的影响。调节c-Src的表达,并评估了对外泌体分泌和EMT启动的影响。c-Src在促进EMT进程的NSCLC标本和NSCLC细胞中水平较高。c-Src的抑制抑制了外泌体的分泌。来自转移性NSCLC细胞的外泌体增强了原代NSCLC细胞的迁移和侵袭能力，具有与c-Src过表达相同的作用。c-Src的抑制抑制实体瘤的生长和转移以及外泌体的分泌，而注射c-Src过表达的外泌体促进肺转移。即使c-Src敲低，TGF-β1也恢复了侵袭和迁移能力。高表达c-Src的转移性NSCLC细胞外泌体可以提高原代NSCLC细胞的c-Src水平,通过TGF-β1途径促进EMT过程。
