2018 Fiscal Year Final Research Report
Functional analysis of IL-17 producing cells in peritoneal metastasis of gastric cancer and examination of its tumorigenecity
| Project/Area Number |
16K10494
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原田 真市 金沢大学, 医学系, 准教授 (90272955)
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| Research Collaborator |
Gunjigake Katsuya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | IL-17A / 肥満細胞 / 胃癌腹膜播種 / STAT3シグナル / 上皮間葉転換 |
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| Outline of Final Research Achievements |
Peritoneal metastasis of gastric cancer induce organ fibrosis, which is reason for poor delivery of chemotherapeutic drug and immunocompetent cells. On the other hand, IL-17A is thought to be involved fibrosis in scleroderma. This study identified which cells produce IL-17A and clarified how IL-17A works in cancer microenvironment. Seventy gastric cancer tissues were immuno-stained using anti-IL-17A Ab and anti-mast cell tryptase (MCT) Ab. The degree of tissue fibrosis was also assessed using Azan staining. As in vitro analysis, the effect of IL-17A on human peritoneal mesothelial cells (HPMCs) was examined. Most of IL-17A positive cells also expressed MCT. There was a significant correlation between double positive cell counts and degree of fibrosis. IL-17A decreased E-cadherin expression, increased alpha-SMA expression and invasion ability in HPMCs through enhancement of STAT3 phosphorylation.
IL-17A contributes EMT in gastric cancer progression and tumor fibrosis.
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| Free Research Field |
消化器外科学
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| Academic Significance and Societal Importance of the Research Achievements |
胃癌腹膜播種の1年生存率は10-40％と極めて不良である。その原因として、腫瘍内には多くの線維成分を含み、癌細胞以外の腫瘍関連線維芽細胞 (CAF)や腫瘍関連マクロファージの存在によって様々なサイトカインが産生され、腫瘍の増殖や進展に関与している。線維化はサイトカインの１つであるTGF-betaがCAFを刺激してコラーゲンファイバーを産生させることが原因と考えられてきたが、今回、腫瘍内に浸潤した肥満細胞から産生されるIL-17AがTGF-betaシグナルとは別のSTAT3シグナルを介して線維化を生じることを明らかにした。腹膜播種の治療標的分子を新たに発見したことで、治療法の開発が期待される。
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