Inhibitory role of Gas6-mediated innate immunity in intestinal tumorigenesis

• Project/Area Number: 23590937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: SENO Hiroshi 京都大学, 医学(系)研究科(研究院), 講師 (90335266)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 大腸 / 腸炎 / 腫瘍 / マウス / マクロファージ / 癌 / 炎症 / 大腸癌 / 自然免疫

Research Abstract

Commensal microbiota affects on the maintenance of systemic homeostasis by the interaction with innate immune cells. Growth arrest specific gene 6 (Gas6) regulates innate immune responses through Stat1/3 signaling. Genetic deletion of Gas6 ameliorated inflammation and tumor formation in the mouse intestines caused by AOM/DSS treatment or insertion of Apc gene mutation. Gas6 knockout mice with intestinal tumors showed significantly shorter survival compared to wild type littermates. As well, colorectal cancer patients with lower Gas6 expression showed shorter survival. These data suggested the importance of innate immunity in the treatment of colorectal cancer.

Research Products

• [Journal Article] Inhibitory Role of Gas6 in Intestinal Tumorigenesis. (2013)
  • Author(s): Yuki Nakanishi, et. al.
  • Journal Title: Carcinogenesis Volume: (印刷中) Issue: 7 Pages: 1567-1574
  • DOI: 10.1093/carcin/bgt069
  • Peer Reviewed
• [Journal Article] Dclk1 distinguishes between tumor and normal stem cells in the intestine. (2013)
  • Author(s): Yuki Nakanishi, et. al.
  • Journal Title: Nature Genetics Volume: 45 Issue: 1 Pages: 98-103
  • DOI: 10.1038/ng.2481
  • Peer Reviewed
• [Journal Article] The role of Hes genes in intestinaldevelopment, homeostasis and tumorformation (2012)
  • Author(s): Ueo T, Imayoshi T, Kobayashi T, OhtsukaT, Seno H, Nakae H, Chiba T, Kageyama R
  • Journal Title: Development Volume: 139 Issue: 6 Pages: 1071-1082
  • DOI: 10.1242/dev.069070
  • Peer Reviewed
• [Journal Article] Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signaling via enhanced ectodomain shedding of TNF-a (2012)
  • Author(s): Kanda K, Komekado H, Kawada M, et al
  • Journal Title: EMBO Molecular Medicine Volume: (印刷中) Issue: 5 Pages: 396-411
  • DOI: 10.1002/emmm.201200216
  • Peer Reviewed
• [Journal Article] Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer (2012)
  • Author(s): Kawada M, et al
  • Journal Title: Oncogene Volume: (印刷中) Issue: 26 Pages: 3111-3123
  • DOI: 10.1038/onc.2011.498
  • Peer Reviewed
• [Journal Article] COX-2 inhibition alters the phenotype of tumor associated macrophages from M2 to M1 in ApcMin/+ mouse polyps (2011)
  • Author(s): Nakanishi Y, Seno H, Kawada M, et al
  • Journal Title: Carcinogenesis Volume: 32(9) Issue: 9 Pages: 1333-1339
  • DOI: 10.1093/carcin/bgr128
  • Peer Reviewed
• [Journal Article] Indigenous Clostridium Species regulate systemic immune responses by induction of colonic regulatory T cells. (2011)
  • Author(s): Chiba T, Seno H.
  • Journal Title: Gastroenterology Volume: 141 Issue: 3 Pages: 1114-1116
  • DOI: 10.1053/j.gastro.2011.07.013
• [Presentation] Dclk1 discriminates between tumor and normal stem cells in the intestine.シンポジウムがん幹細胞研究に基づく新たながん治療戦略 (2013)
  • Author(s): 妹尾浩, 中西祐貴, 千葉勉
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸神戸国際会議場
  • Year and Date: 2013-12-04
• [Presentation] 腸腫瘍幹細胞特異的マーカーDclk1の同定. International Sessionsがん幹細胞 (2013)
  • Author(s): 中西祐貴, 上尾太郎, 妹尾浩
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2013-10-04
• [Presentation] Intestinal tumors are continuously renewed by Dclk1-positive tumor stem cells (2013)
  • Author(s): Nakanishi Y, Seno H, Chiba T
  • Organizer: American Association of Cancer Research, Annual Meeting 2013
  • Place of Presentation: Washington DC, USA, Walter E. Washington Convention Center
  • Year and Date: 2013-04-10
• [Presentation] 正常腸管および腸腫瘍におけるDclk1/Lgr5陽性細胞の役割 (2013)
  • Author(s): 中西祐貴, 妹尾浩, 上尾太郎
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 鹿児島かごしま県民交流センター
  • Year and Date: 2013-03-23
• [Presentation] The role of Dclk1-positive cells in the intestinal homeostasis (2012)
  • Author(s): Nakanishi Y, Seno H, Ueo T, Chiba T
  • Organizer: 2012 James W. Freston Single Topic Conference : Gastrointestinal Stem Cell Biology and Pathobiology
  • Place of Presentation: Chicago, USA, Intercontinental Hotel Chicago
  • Year and Date: 2012-08-27
• [Presentation] Dclk1 discriminates between tumor and normal stem cells in the intestine (2012)
  • Author(s): Seno H
  • Organizer: GI Research Academy 2012
  • Place of Presentation: Tokyo, Japan, Keidanren Hall
  • Year and Date: 2012-06-15
• [Presentation] 腸腫瘍幹細胞特異的マーカーDcamkl1の同定 (2012)
  • Author(s): 中西祐貴, 上尾太郎, 妹尾浩
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京京王プラザホテル
  • Year and Date: 2012-04-20
• [Presentation] Hes1は大腸上皮細胞の位置を規定し, ニッチ由来のWntやBMPシグナルによる分化制御に関与する (2012)
  • Author(s): 上尾太郎, 妹尾浩, 仲瀬裕志:
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京京王プラザホテル
  • Year and Date: 2012-04-19
• [Presentation] ナルディライジンはTNF-αのシェディングを促進し内因性サイトカインシグナル経路を活性化して胃癌細胞の増殖を制御する (2011)
  • Author(s): 神田啓太郎、米門秀行、妹尾浩、千葉勉、西英一郎
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
• [Presentation] 腸腫瘍幹細胞特異的マーカーDcamkl1の同定
  • Author(s): 中西祐貴
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都）
• [Book] Proton pump inhibitors and gastrointestinal side effects. Proton Pump Inhibitors : A Balanced View. Front Gastrointest Res. Vol.32 (2013)
  • Author(s): Nakamura S, Seno H, Chiba T (Chiba T, Malfertheiner P, Satoh H (eds))
  • Publisher: Basel, Karger