The role of human peritoneal mesothelial cells in the fibrosis and progression of gastric cancer.
The role of human peritoneal mesothelial cells in the fibrosis and progression of gastric cancer.
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DOI：
10.3892/ijo.2012.1490
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发表时间：
2012-08
影响因子：
5.2
通讯作者：
Ohta T
中科院分区：
文献类型：
--
作者：
Tsukada T;Fushida S;Harada S;Yagi Y;Kinoshita J;Oyama K;Tajima H;Fujita H;Ninomiya I;Fujimura T;Ohta T
腹膜播散是硬化性胃癌最常见的转移方式。然而，尽管进行了广泛的研究，但疾病的结果并没有得到充分的改善。肿瘤进展和转移由癌症与基质中的各种细胞（包括内皮细胞、免疫细胞和成纤维细胞）之间的相互作用引起。成纤维细胞已得到特别深入的研究;已知它们会转变为癌相关成纤维细胞（CAF）并产生转化生长因子β（TGF-β），后者介导癌症-间质相互作用。在这里，我们研究了来源于腹膜微环境中的癌细胞的TGF-β是否激活人腹膜间皮细胞（HPMCs），导致胃癌的进展和纤维化。结果发现，活化的HPMCs（a-HPMCs）呈梭形，E-cadherin表达减少，α-SMA表达增加。此外，在直接细胞-细胞接触后，a-HPMCs变得更具侵袭性并上调人胃癌衍生的MKN 45细胞的增殖。值得注意的是，与a-HPMCs共培养的MKN 45细胞在体外也获得了非贴壁依赖性细胞生长并降低了E-钙粘蛋白的表达。为了测量体内共培养的效果，我们开发了小鼠异种移植模型，其中皮下注射不同的培养产物。在给予与a-HPMC共培养的MKN 45细胞的小鼠中观察到最大的肿瘤。此外，这些肿瘤含有HPMC衍生的纤维组织。因此，上皮间质转化（EMT）的HPMCs似乎驱动腹膜传播和肿瘤纤维化。
Peritoneal dissemination is the most frequent metastatic pattern of scirrhous gastric cancer. However, despite extensive research effort, disease outcomes have not improved sufficiently. Tumor progression and metastasis result from interactions between cancer and various cells in the stroma, including endothelial cells, immune cells and fibroblasts. Fibroblasts have been particularly well studied; they are known to change into carcinoma-associated fibroblasts (CAFs) and produce transforming growth factor β (TGF-β), which mediates cancer-stroma interactions. Here, we investigated whether TGF-β derived from cancer cells in the peritoneal microenvironment activates human peritoneal mesothelial cells (HPMCs), leading to the progression and fibrosis of gastric cancer. We found that activated HPMCs (a-HPMCs) took on a spindle shape formation, decreased the expression of E-cadherin and increased that of α-SMA. Furthermore, a-HPMCs became more invasive and upregulated proliferation of human gastric cancer-derived MKN45 cells following direct cell-cell contact. Notably, MKN45 cells co-cultured with a-HPMCs also acquired anchorage-independent cell growth and decreased expression of E-cadherin in vitro. To measure the effects of the co-culture in vivo, we developed a mouse xenograft model into which different culture products were subcutaneously injected. The largest tumors were observed in mice that had been given MKN45 cells co-cultured with a-HPMCs. Furthermore, these tumors contained HPMC-derived fibrous tissue. Thus, the epithelial-mesenchymal transition (EMT) of HPMCs appears to drive peritoneal dissemination and tumor fibrosis.
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影响因子：
14.5
作者：
Tlsty, TD
通讯作者：
Tlsty, TD
影响因子：
3
作者：
Yonemura, Yutaka;Elnemr, Ayman;Li, Yan
通讯作者：
Li, Yan
影响因子：
3.6
作者：
Kajiyama, Hiroaki;Shibata, Kiyosumi;Kikkawa, Fumitaka
通讯作者：
Kikkawa, Fumitaka
影响因子：
6.4
作者：
YOSHIDA, K;YOKOZAKI, H;TAHARA, E
通讯作者：
TAHARA, E
DOI：
10.1152/ajpgi.2000.279.5.g845
发表时间：
2000-11-01
影响因子：
4.5
作者：
Wells, RG
通讯作者：
Wells, RG