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

被引：99

作者：

Deng, Guang ^{[1
]}

Qu, Jinglei ^{[1
]}

Zhang, Ye ^{[1
]}

Che, Xiaofang ^{[1
]}

Cheng, Yu ^{[1
]}

Fan, Yibo ^{[1
]}

Zhang, Simeng ^{[1
]}

Na, Di ^{[2
]}

Liu, Yunpeng ^{[1
]}

Qu, Xiujuan ^{[1
]}

机构：

[1] China Med Univ, Hosp 1, Dept Med Oncol, Shenyang, Liaoning, Peoples R China

[2] China Med Univ, Hosp 1, Dept Surg Oncol, Shenyang, Liaoning, Peoples R China

来源：

FEBS LETTERS | 2017年 / 591卷 / 14期

基金：

中国国家自然科学基金;

关键词：

exosome; gastric cancer; mesothelial barrier destruction; peritoneal mesothelial cell; peritoneal metastasis; TO-MESENCHYMAL TRANSITION; CARCINOMA-ASSOCIATED-FIBROBLASTS; INDUCED APOPTOSIS; EXTRACELLULAR VESICLES; PREMETASTATIC NICHE; CELL MORPHOLOGY; OVARIAN-CANCER; BREAST-CANCER; IN-VITRO; DISSEMINATION;

D O I：

10.1002/1873-3468.12722

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2167 / 2179

页数：13

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