Deng Guang, Qu Jinglei, Zhang Ye, Che Xiaofang, Cheng Yu, Fan Yibo, Zhang Simeng, Na Di, Liu Yunpeng, Qu Xiujuan
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
FEBS Lett. 2017 Jul;591(14):2167-2179. doi: 10.1002/1873-3468.12722. Epub 2017 Jul 10.
An intact mesothelium serves as a protective barrier to inhibit peritoneal carcinomatosis. Cancer-derived exosomes can mediate directional tumor metastasis; however, little is known about whether gastric cancer-derived exosomes will destroy the mesothelial barrier and promote peritoneal dissemination. Here, we demonstrate that gastric cancer-derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis. Injury of peritoneal mesothelial cells elicited by gastric cancer-derived exosomes is through concurrent apoptosis and mesothelial-to-mesenchymal transition (MMT). Additionally, upregulation of p-ERK in peritoneal mesothelial cells is primarily responsible for the MMT while contributing little to apoptosis. Together, these data support the concept that exosomes play a crucial role in remodeling the premetastatic microenvironment and identify a novel mechanism for peritoneal metastasis of gastric carcinoma.
完整的间皮作为一种保护屏障可抑制腹膜癌转移。癌症来源的外泌体可介导肿瘤的定向转移；然而，关于胃癌来源的外泌体是否会破坏间皮屏障并促进腹膜播散，目前所知甚少。在此，我们证明胃癌来源的外泌体通过引起间皮屏障破坏和腹膜纤维化促进腹膜转移。胃癌来源的外泌体引发的腹膜间皮细胞损伤是通过同时发生的细胞凋亡和间皮-间质转化（MMT）实现的。此外，腹膜间皮细胞中p-ERK的上调主要负责MMT，而对细胞凋亡的作用很小。总之，这些数据支持了外泌体在重塑转移前微环境中起关键作用的概念，并确定了胃癌腹膜转移的一种新机制。
