Progression of the gastric cancer using novel mouse spontaneously developed differentiated type adenocarcinoma

• Project/Area Number: 16K08708
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Shinshu University
• Principal Investigator: Kawakubo Masatomo 信州大学, 学術研究院医学系, 講師 (70397305)
• Co-Investigator(Kenkyū-buntansha): 中山 淳 信州大学, 学術研究院医学系, 教授 (10221459)
• Research Collaborator: Arisaka Nobuhiko ; Miyashita Masaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: A4gnt欠損マウス / 胃癌 / ピロリ菌 / エピジェネティック / ピロリ菌感染 / αGlcNAc / 胃粘液 / 好中球 / 胃癌発生 / 胃癌発生機序 / モデルマウス / 胃粘膜糖鎖

Outline of Final Research Achievements

Infection with Helicobacter pylori is the major cause of gastric cancer. Mice deficient in αGlcNAc contained in gastric mucin, which has tumor suppressor function in differentiated type adenocarcinoma, were infected with H. pylori to investigate the molecular mechanism of tumorigenesis prior to gastric cancer development. We obtained new findings on epigenetic changes mainly in microRNA expression analysis related with the pathological findings depending on H. pylori infection.Although the progression of differentiated type adenocarcinoma on A4gnt KO mice was not fully clear by pathological or molecular processes related to H. pylori infection in the lack of αGlcNAc on gastric gland mucin, it was shown that severe gastric erosion occurred in A4gnt KO mice infected with H. pylori due to mucosal infiltration with neutrophils.

Academic Significance and Societal Importance of the Research Achievements

A4gnt KOマウスにピロリ菌感染を生じさせることは，胃癌発生の要因となり得るヒトの体質のような，癌化リスクを基本要素として持つ基盤に，胃癌の主因であるピロリ菌感染をモデル化できると期待される実験系であり，ピロリ菌初感染から胃粘膜上皮細胞の不可逆的な変成をきたす過程を解明し，より効果的に癌化リスクを減らすピロリ菌除菌のタイミングを見いだせるものと思われる．

Research Products

• [Journal Article] Cholesterol-α-glucosyltransferase gene is present in most Helicobacter species including gastric non-Helicobacter pylori helicobacters obtained from Japanese patients. (2018)
  • Author(s): Kawakubo M, Horiuchi K, Matsumoto T, Nakayama J, Akamatsu T, Katsuyama T, Ota H, Sagara J
  • Journal Title: Helicobacter Volume: 23 Issue: 1
  • DOI: 10.1111/hel.12449
  • Peer Reviewed / Open Access
• [Journal Article] Cloning of Helicobacter suis cholesterol α-glucosyltransferase and production of an antibody capable of detecting it in formalin-fixed, paraffin-embedded gastric tissue sections, (2017)
  • Author(s): Masatomo Kawakubo, Kazuki Horiuchi, Hitomi Komura, Yoshiko Sato, Masayoshi Kato, Meguru Ikeyama, Mana Fukushima, Shigenori Yamada, Satoshi Ishizone, Takehisa Matsumoto, Hiroyoshi Ota, Junji Sagara, Jun Nakayama
  • Journal Title: Histochemistry and Cell Biology Volume: 印刷中 Issue: 4 Pages: 463-471
  • DOI: 10.1007/s00418-017-1582-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ホルマリン固定パラフィン包埋切片を用いた免疫染色に有用なハイルマーニ菌特異抗体の樹立 (2016)
  • Author(s): 川久保 雅友，佐藤 佳子，小村 仁美，池山 環，福島 万奈，太田 浩良，相良 淳二，中山 淳
  • Organizer: 第57回日本組織細胞化学会学術集会
  • Place of Presentation: 東京都, 三鷹市，杏林大学 井の頭キャンパス
  • Year and Date: 2016-09-03
• [Remarks] 信州大学医学部医学科・大学院総合医理工学研究科医学系専攻医学分野 分子病理学教室
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/chair/i-2byori/work.html
• [Remarks] 信州大学大学院医学系研究科分子病理学教室 -論文など-
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/chair/i-2byori/work.html