Gastric cancer‐derived exosomes promote peritoneal metastasis by destroying the mesothelial barrier

• Published in: FEBS letters Vol. 591; no. 14; pp. 2167 - 2179
• Main Authors: Deng, Guang, Qu, Jinglei, Zhang, Ye, Che, Xiaofang, Cheng, Yu, Fan, Yibo, Zhang, Simeng, Na, Di, Liu, Yunpeng, Qu, Xiujuan
• Format: Journal Article
• Language: English
• Published: England 01.07.2017
• Subjects: Apoptosis; carcinoma; Cell Line, Tumor; Epithelium - pathology; exosome; exosomes; Exosomes - pathology; fibrosis; gastric cancer; Humans; MAP Kinase Signaling System; Mesoderm - pathology; mesothelial barrier destruction; metastasis; peritoneal mesothelial cell; peritoneal metastasis; Peritoneal Neoplasms - secondary; Stomach Neoplasms - pathology; peritoneal mesothelial cell; mesothelial barrier destruction; gastric cancer; exosome; peritoneal metastasis
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1002/1873-3468.12722

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.