Miao Zhi-Feng, Zhao Ting-Ting, Wang Zhen-Ning, Miao Feng, Xu Ying-Ying, Mao Xiao-Yun, Gao Jian, Xu Hui-Mian
Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, No.155 North Nanjing Street, Heping District, Shenyang, Liaoning Province, China, 110001.
Tumour Biol. 2014 Jun;35(6):6105-11. doi: 10.1007/s13277-014-1808-1. Epub 2014 Mar 11.
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 (both p<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 (both p<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 (both p<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.
腹膜播散在胃癌中极为常见。人腹膜间皮细胞（HPMC）屏障受损会引发胃癌腹膜播散（GCPD），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，我们研究了腹膜中纤维母细胞活化蛋白（FAP）表达与原发性肿瘤病理特征之间的关联。根据FAP表达评估胃癌患者的临床预后。在胃癌细胞 - HPMC共培养系统中，通过蛋白质免疫印迹法评估E - 钙黏蛋白、α - 平滑肌肌动蛋白和FAP的表达。还检测了胃癌细胞向HPMC的迁移和黏附情况。我们的结果显示，86例中有36例（41.9%）腹膜FAP染色呈阳性，这与原发性胃癌的较高TNM分期以及GCPD的较高发生率相关（均p<0.05）。生存分析表明FAP表达是生存不良的独立预后因素（p = 0.02）。FAP阳性表达的腹膜呈现出明显的纤维化发展，并表达更高水平的间充质标志物α - SMA，这在体外蛋白质免疫印迹试验中得到证实。在HPMC与胃癌细胞黏附试验中，SGC - 7901细胞在不同细胞密度下更倾向于黏附TA - HPMC（均p<0.05）。此外，与与正常胃腺上皮细胞共培养的HPMC相比，SGC - 7901细胞更易于被表达FAP的肿瘤相关人腹膜间皮细胞（TA - HPMC）以时间依赖性方式趋化（均p<0.05）。我们的研究表明腹膜FAP表达与GCPD之间存在正相关。表达FAP的TA - HPMC可能是GCPD的重要细胞成分和诱因。
