Endoglin overexpression mediates gastric cancer peritoneal dissemination by inducing mesothelial cell senescence

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• 作者：Zhi-Feng Miao ; MD^a ; ¹ ; Jian-Hua Wu ; MD^a ; ¹ ; Zhen-Ning Wang ; MD^a ; Ting-Ting Zhao ; MD^b ; Hui-Mian Xu ; MD^a ; Yong-Xi Song ; MD^a ; Ya-Nan Xing ; MD^a ; Jin-Yu Huang ; MD^a ; Jun-Yan Zhang ; MD^a ; Xing-Yu Liu ; MD^a ; Hao Xu ; MD^a ; Ying-Ying Xu ; MD^b ; ^{13898829926@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Stomach cancer ; Peritoneal dissemination ; Mesothelial cell ; Senescence ; Endoglin ; TGF-β receptor
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：51
• 期：Complete
• 页码：114-123
• 全文大小：1072 K

文摘

Peritoneal dissemination (PD), which is highly frequent in gastric cancer (GC) patients, is the main cause of death in advanced GC. Senescence of human peritoneal mesothelial cells (HPMC) may contribute to GC peritoneal dissemination (GCPD). In this study of 126 patients, we investigated the association between Endoglin expression in GC peritoneum and the clinicopathological features. The prognosis of patients was evaluated according to Endoglin and ID1 expression. In vitro, GC cell (GCC)–HPMC coculture was established. Endoglin and ID1 expression was evaluated by Western blot. Cell cycle and HPMC senescence were analyzed after harvesting HPMC from the coculture. GCC adhesion and invasion to HPMC were also assayed. Our results showed that positive staining of Endoglin (38%) was associated with a higher TNM stage and higher incidence of GCPD (both P < .05). Kaplan-Meier analysis showed that the patients who were Endoglin positive had a shorter survival time compared with Endoglin-negative patients (P = .02). Using the HPMC and GCC adherence and invasion assay, we demonstrated that transforming growth factor beta 1 (TGF-β)1–induced HPMC senescence was attenuated by silencing the Endoglin expression, which also prevented GCC attachment and invasion. Our study indicated a positive correlation between Endoglin overexpression and GCPD. Up-regulated Endoglin expression induced HPMC senescence via TGF-β1 pathway. The findings suggest that Endoglin-induced HPMC senescence may contribute to peritoneal dissemination of GCCs.