TY - JOUR AB - 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. AD - Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan Center for Biomedical Research and Education, School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan AU - Tsukada,Tomoya AU - Fushida,Sachio AU - Harada,Shinichi AU - Yagi,Yasumichi  AU - Kinoshita,Jun  AU - Oyama,Katsunobu AU - Tajima,Hidehiro AU - Fujita,Hideto  AU - Ninomiya,Itasu AU - Fujimura,Takashi AU - Ohta,Tetsuo DA - 2012/08/01 DO - 10.3892/ijo.2012.1490 EP - 482 IS - 2 JO - Int J Oncol KW - gastric cancer human peritoneal mesothelial cell fibrosis epithelial-mesenchymal transition cell-cell interaction PY - 2012 SN - 1019-6439 1791-2423 SP - 476 ST - The role of human peritoneal mesothelial cells in the fibrosis and progression of gastric cancer T2 - International Journal of Oncology TI - The role of human peritoneal mesothelial cells in the fibrosis and progression of gastric cancer UR - https://doi.org/10.3892/ijo.2012.1490 VL - 41 ER -