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.
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.