Tumor-associated mesothelial cells are negative prognostic factors in gastric cancer and promote peritoneal dissemination of adherent gastric cancer cells by chemotaxis
Tumor-associated mesothelial cells are negative prognostic factors in gastric cancer and promote peritoneal dissemination of adherent gastric cancer cells by chemotaxis
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肿瘤相关间皮细胞是胃癌的负面预后因素，并通过趋化作用促进贴壁胃癌细胞的腹膜播散
DOI：
10.1007/s13277-014-1808-1
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发表时间：
2014-06-01
期刊：
影响因子：
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通讯作者：
Xu, Hui-Mian
中科院分区：
文献类型：
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作者：
Miao, Zhi-Feng;Zhao, Ting-Ting;Xu, Hui-Mian
腹膜扩散在胃癌中是非常常见的。人腹膜间皮细胞(HPMC)屏障的损伤可导致胃癌腹膜扩散(GCPD)，GCPD是GCPD过程中的关键事件，以成纤维细胞发育为特征。在本研究中，我们研究了腹膜成纤维细胞激活蛋白(FAP)的表达与原发肿瘤病理特征的关系。根据FAP的表达评估胃癌患者的临床预后。采用免疫印迹法检测E-钙粘附素、α-平滑肌肌动蛋白和FAP在胃癌细胞-HPMC共培养体系中的表达。检测胃癌细胞对HPMC的迁移和黏附能力。86例患者中36例腹膜FAP染色阳性(41.9%)，与原发癌的高TNM分期和GCPD的发生率有关(P和 均为0.05)。生存分析显示，FAP表达是预后不良的独立预后因素(p= 0.02)。体外Western印迹实验证实，FAP阳性表达的腹膜有明显的纤维化发展，且间充质标志物α-SMA的表达水平较高。在HPMC和胃癌细胞黏附实验中，SGC7901细胞在不同的细胞密度下优先黏附于TA-HPMC(均为 )。此外，与正常胃腺上皮细胞共培养相比，表达FAP的肿瘤相关人腹膜间皮细胞(TA-HPMC)对SGC7901细胞的趋化作用更强，且呈时间依赖关系( 均0.05)。我们的研究表明腹膜FAP的表达与GCPD呈正相关。FAP表达的TA-HPMC可能是GCPD的重要细胞成分和促进剂。
Peritoneal dissemination is highly frequent in gastric cancer. Damage to human peritoneal mesothelial cell (HPMC) barriers provokes gastric cancer peritoneal dissemination (GCPD), the key events during GCPD, is characterized by fibroblastic development. In this study, we have studied the association between fibroblast activation protein (FAP) expression in peritoneum and the pathological features of the primary tumor. The clinical prognosis of gastric cancer patients was evaluated according to FAP expression. In a gastric cancer cell-HPMC co-culture system, expression of E-cadherin, α-smooth muscle actin, and FAP were evaluated by Western blotting. Gastric cancer cell migration and adhesion to HPMC were also assayed. Our results showed positive peritoneal staining of FAP in 36/86 cases (41.9 %), which was associated with a higher TNM stage in primary gastric cancer and higher incidence of GCPD (bothp< 0.05). Survival analysis showed FAP expression was an independent prognostic factor of poor survival (p= 0.02). Peritoneum of FAP-positive expression exhibited a distinct fibrotic development and expressed higher level of the mesenchymal marker α-SMA, which was confirmed by the in vitro Western blot assay. In HPMC and gastric cancer cell adherence assay, SGC-7901 cells preferentially adhered to TA-HPMC at different cell densities (bothp< 0.05). Additionally, SGC-7901 cells were more prone to chemotaxis by FAP-expressed tumor-associated–human peritoneal mesothelial cells (TA-HPMC) compared with HPMC co-cultured with normal gastric glandular epithelial cells in a time-dependent manner (bothp< 0.05). Our study indicated a positive correlation between peritoneum FAP expression and GCPD. FAP-expressed TA-HPMC might be an important cellular component and instigator of GCPD.