Hepatocyte Growth Factor Activator Inhibitor Type 1 Is a Suppressor of Intestinal Tumorigenesis

DOI PDF PubMed 被引用文献13件 参考文献49件 オープンアクセス
  • Shinri Hoshiko
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Makiko Kawaguchi
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Tsuyoshi Fukushima
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Yukihiro Haruyama
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Kenji Yorita
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Hiroyuki Tanaka
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Motoharu Seiki
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Haruhiko Inatsu
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Kazuo Kitamura
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Hiroaki Kataoka
    Authors' Affiliations: 1Section of Oncopathology and Regenerative Biology, Department of Pathology, 2Section of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; and 3Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

書誌事項

公開日
2013-04-15
資源種別
journal article
DOI
  • 10.1158/0008-5472.can-12-3337
公開者
American Association for Cancer Research (AACR)

この論文をさがす

説明

<jats:title>Abstract</jats:title> <jats:p>Hepatocyte growth factor activator inhibitor type 1 (HAI-1/SPINT1) is a membrane-bound serine protease inhibitor expressed on the surface of epithelial cells. Although HAI-1/SPINT1 is abundantly expressed in the intestinal epithelium, its role in intestinal tumorigenesis is not known. In this study, we investigated the role of Hai-1/Spint1 in intestinal tumorigenesis using mouse models. The membranous Hai-1/Spint1 immunoreactivity was decreased in murine ApcMin/+ tumors and also in carcinogen (azoxymethane treatment followed by dextran sodium sulfate administration)-induced colon tumors compared with the adjacent non-neoplastic epithelium. The decreased immunoreactivity appeared to be due to sheddase activity of membrane-type 1 matrix metalloprotease. Then, we examined the effect of intestine-specific deletion of Spint1 gene on ApcMin/+ mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods. Activation of HGF was enhanced in Hai-1/Spint1–deficient ApcMin/+ intestine. Gene expression profiling revealed upregulation of the Wnt/β-catenin signaling circuit, claudin-2 expression, and angiogenesis not only in tumor tissue but also in the background mucosa without macroscopic tumors in Hai-1/Spint1–deficient ApcMin/+ intestine. Intestinal deletion of Spint1 also enhanced the susceptibility to carcinogen-induced colon tumorigenicity of wild-type Apc mice. Our findings suggest that HAI-1/SPINT1 has a crucial role in suppressing intestinal tumorigenesis, which implies a novel link between epithelial cell surface serine protease inhibitors and protection from carcinogenic stimuli. Cancer Res; 73(8); 2659–70. ©2013 AACR.</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 73 (8), 2659-2670, 2013-04-15

    American Association for Cancer Research (AACR)

被引用文献 (13)*注記

もっと見る

参考文献 (49)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ