Abstract
Abstract
Objectives
Interleukin-17A (IL-17A) is pro-inflammatory cytokine and acts as profibrotic factor in the fibrosis of various organs. Fibrosis tumor-like peritoneal dissemination of gastric cancer interferes with drug delivery and immune cell infiltration because of its high internal pressure. In this study, we examined the relationship between IL-17A and tissue fibrosis in peritoneal dissemination and elucidated the mechanism of fibrosis induced by IL-17A using human peritoneal mesothelial cells (HPMCs) and a mouse xenograft model.
Methods
Seventy gastric cancer patients with peritoneal dissemination were evaluated. The correlation between IL-17A and fibrosis was examined by immunofluorescence and immunohistochemistry. A fibrosis tumor model was developed based on subcutaneous transplantation of co-cultured cells (HPMCs and human gastric cancer cell line MKN-45) into the dorsal side of nude mice. Mice were subsequently treated with or without IL-17A. We also examined the effect of IL-17A on HPMCs in vitro.
Results
There was a significant correlation between IL-17A expression, the number of mast cell tryptase (MCT)-positive cells, and the degree of fibrosis (r = 0.417, P < 0.01). In the mouse model, IL-17A enhanced tumor progression and fibrosis. HPMCs treated with IL-17A revealed changes to a spindle-like morphology, decreased E-cadherin expression, and increased α-SMA expression through STAT3 phosphorylation. Moreover, HPMCs treated with IL-17A showed increased migration.
Conclusions
IL-17A derived from mast cells contributes to tumor fibrosis in peritoneal dissemination of gastric cancer. Inhibiting degranulation of mast cells might be a promising treatment strategy to control organ fibrosis.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Gastroenterology,Oncology,General Medicine
Reference41 articles.
1. Yamazaki H, Oshima A, Murakami R, Endoh S, Ubukata T. Long-term follow-up study of patients with gastric cancer detected by mass screening. Cancer. 1989;63:613–7.
2. Chen CY, Wu CW, Lo SS, Hsieh MC, Lui WY, Shen KH. Peritoneal carcinomatosis and lymph node metastasis are prognostic indicators in patients with Borrmann type IV gastric carcinoma. Hepatogastroenterology. 2002;49:874–7.
3. Japanese Gastric Cancer Association Registration Committee, Maruyama K, Kaminishi M, Hayashi K, Isobe Y, Honda I, et al. Gastric cancer treated in 1991 in Japan: data analysis of nationwide registry. Gastric Cancer. 2006;9:51–66.
4. Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ. Gastric cancer. Lancet. 2009;374:477–90.
5. Fushida S, Kinoshita J, Yagi Y, Funaki H, Kinami S, Ninomiya I, et al. Dual anti-cancer effects of weekly intraperitoneal docetaxel in treatment of advanced gastric cancer patients with peritoneal carcinomatosis: a feasibility and pharmacokinetic study. Oncol Rep. 2008;19:1305–10.
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