Tissue-specific trafficking of immune-competent cells mediated by lymph node-associated cell trafficking signals and regulation of immune-responses towards self components.

• Project/Area Number: 25460603
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Hyogo University of Health Sciences
• Principal Investigator: TANAKA Toshiyuki 兵庫医療大学, 薬学部, 教授 (30217054)
• Co-Investigator(Kenkyū-buntansha): UEDA Haruyasu 兵庫医療大学, 薬学部, 教授 (10330458) ; OHNO Yoshiya 兵庫医療大学, 薬学部, 助教 (40509155)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 免疫学 / 細胞動員 / 血管内細胞 / 自然免疫 / 獲得免疫 / 微小環境 / 細胞接着分子 / サイトカイン

Outline of Final Research Achievements

Tissue-specific trafficking of immune-competent cells controls their reactivity towards self components. In this study, we found followings; 1) endothelial cell adhesion molecule nepmucin/CD300LG was constitutively expressed in the small arterioles, venules, and capillaries of most tissues, but was barely detectable in those of immunologically privileged sites. The nepmucin/CD300LG expression rapidly decreased in lymph nodes acute inflammatory response or tumor growth, suggesting that nepmucin/CD300LG expression was negatively regulated by locally produced signals under these circumstances, and 2) malignant mesothelioma (MM) cells formed multicellular spheroid in which ALDH-expressing cancer stem-like cells were enriched. The CD44-HA axis and Activin-A/ALK4 axis differentially regulated spheroid formation and maintenance of ALDH-expressing cancer stem-like cell in MM spheroids, respectively.

Research Products

• [Journal Article] Suppression of SOX7 by DNA methylation and its tumor suppressor function in acute myeloid leukemia. (2015)
  • Author(s): Man CH, Fung TK, Wan H, Cher CY, Fan A, Ng N, Ho C, Wan TS, Tanaka T, So CW, Kwong YL, Leung AY.
  • Journal Title: Blood Volume: 125 Issue: 25 Pages: 3928-3936
  • DOI: 10.1182/blood-2014-06-580993
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dynamic changes in endothelial cell adhesion molecule nepmucin/CD300LG expression under physiological and pathological conditions. (2013)
  • Author(s): Umemoto, E, Takeda, A., Jin, S., Luo, Z., Nakahogi, N., Hayasaka, H., Lee, C.M., Tanaka, T. & Miyasaka, M.
  • Journal Title: PLoS One Volume: 8 Issue: 12 Pages: 1-12
  • DOI: 10.1371/journal.pone.0083681
  • Peer Reviewed
• [Presentation] 低酸素環境が造腫瘍性を示すCD133陽性悪性中皮腫細胞の維持に寄与する. (2015)
  • Author(s): 大野喜也、田中稔之
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Activin-ALK4 axisは悪性中皮腫細胞株MSTOのALDHhigh細胞を維持し、造腫瘍性を高める. (2015)
  • Author(s): 大野喜也、田中稔之
  • Organizer: 第24回日本がん転移学会学術集会・総会
  • Place of Presentation: シティプラザ大阪（大阪府大阪市）
  • Year and Date: 2015-07-23
• [Presentation] THP-1 macrophage-like cells were induced to differentiate towards an M2-like phenotype by human malignant mesothelioma cells and enhanced the expression of stem cell-associated markers in the tumor cells. (2015)
  • Author(s): Ohno Y, Tanaka T.
  • Organizer: International Conference of Cancer Immunotherapy and Macrophages 2015
  • Place of Presentation: Ito International Research Center（東京都文京区）
  • Year and Date: 2015-07-09
  • Int'l Joint Research
• [Presentation] CD44依存的なスフェロイド形成はactivin産生を介してALDH発現を亢進させる. (2014)
  • Author(s): 大野喜也、田中稔之
  • Organizer: 第23回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢市文化ホール（石川県金沢市）
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] CD44-dependent signals and pro- and anti-inflammatory cytokines differentially regulate spheroid formation and maintenance of cancer stem-like cells in malignant mesothelioma cells. (2014)
  • Author(s): 大野喜也、田中稔之
  • Organizer: 第22回マクロファージ分子細胞生物学国際シンポジウム（MMCB2014）
  • Place of Presentation: 神戸商工会議所（兵庫県神戸市）
  • Year and Date: 2014-06-02 – 2014-06-03
• [Presentation] Spheroid forming malignant mesothelioma cells showed cancer stem cell-like properties and spontaneously produced proinflammatory cytokines
  • Author(s): 大野喜也、牛尾明雅、田中亜弥、筆坂世奈、新玉紗理奈、三宅咲奈、上田晴康、田中稔之
  • Organizer: 第21回マクロファージ分子細胞生物学国際シンポジウム（MMCB2013）
  • Place of Presentation: 都市センターホテル（東京都千代田区）
• [Presentation] TGFシグナルによる悪性中皮腫スフェロイドの形成とALDH陽性癌幹細胞様細胞の制御
  • Author(s): 大野喜也、筆坂世奈、清水雄太、三宅咲奈、田中稔之
  • Organizer: 第22回日本がん転移学会学術集会・総会
  • Place of Presentation: ホテルブエナビスタ（長野県松本市）
• [Presentation] HA-CD44 axis was required for formation of malignant mesothelioma spheroids and maintenance of CSC-like ALDHhigh cells
  • Author(s): 大野喜也、田中稔之
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] 悪性中皮腫のスフェロイド形成とALDH陽性癌幹細胞様細胞におけるActivinの役割
  • Author(s): 清水雄太、大野喜也、田中稔之
  • Organizer: 第63回日本薬学会近畿支部総会・大会
  • Place of Presentation: 同志社女子大学（京都府京田辺市）
• [Presentation] 悪性中皮腫のスフェロイド形成と癌幹細胞様細胞におけるActivinの役割
  • Author(s): 清水雄太、大野喜也、田中稔之
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本市総合体育館（熊本県熊本市）
• [Book] Encyclopedia of Immunobiology, Vol. 3 (2016)
  • Author(s): Ratcliffe, M.J.H. (Editor in Chief) ; Tanaka T.
  • Total Pages: 536
  • Publisher: Academic Press
• [Book] 標準生理学 第８版 (2014)
  • Author(s): 田中稔之、大橋俊夫、北川誠一、石川義弘、本間研一、丸中良典、木村純子、瀬尾義輝、久保義弘、岡村康司、飯野正光、柚﨑通介、真鍋俊也、玉巻伸章、金子武嗣、河野憲二、泰羅雅登、吉村 惠、大森治紀、杉内友理子 他
  • Total Pages: 1140
  • Publisher: 医学書院