Functional analysis of CD109 in Brain Tumor.

• Project/Area Number: 18K15116
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Nagoya University
• Principal Investigator: Shiraki Yukihiro 名古屋大学, 医学系研究科, 助教 (40804753)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: CD109 / 脳腫瘍 / 病理学 / 神経膠腫/膠芽腫 / 脳腫瘍幹細胞 / 治療抵抗性

Outline of Final Research Achievements

We identified latent TGF-β binding protein-1 (LTBP1) as a CD109-interacting protein using mass spectrometry and confirmed their interaction by co-immunoprecipitation. CD109 expression enhanced TGF-β activation in the presence of LTBP1.
Although we tried to develop antibody drug against CD109, we could not obtain notarizing antibody or antibody with ADCC activity.

Academic Significance and Societal Importance of the Research Achievements

CD109は様々な腫瘍で悪性化・進展に関わる分子であるが、今回新たにCD109がLTBP1に対して結合して、TGF-β活性化を促進するという機能を発見した。CD109を発現する腫瘍細胞と周囲の微小環境との関りを研究する上で重要な知見が得られたと考えている。

Research Products

• [Journal Article] CD109 regulates in vivo tumor invasion in lung adenocarcinoma through TGF-β signaling. (2020)
  • Author(s): Taki T, Shiraki Y, Enomoto A, Weng L, Chen C, Asai N, Murakumo Y, Yokoi K, Takahashi M, Mii S.
  • Journal Title: Cancer Sci. Volume: 111 Issue: 12 Pages: 4616-4628
  • DOI: 10.1111/cas.14673
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis. (2019)
  • Author(s): Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Yamaguchi J, Wang T, Woods SL, Worthley D, Shimamura T, Fujishiro M, Hirooka Y, Enomoto A, Takahashi M. et al.
  • Journal Title: Cancer Res. Volume: 79 Issue: 20 Pages: 5367-5381
  • DOI: 10.1158/0008-5472.can-19-0454
  • NAID: 120006786261
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD109: a multifunctional GPI-anchored protein with key roles in tumor progression and physiological homeostasis. (2019)
  • Author(s): Mii S, Enomoto A, Shiraki Y, Taki T, Murakumo Y, Takahashi M.
  • Journal Title: Pathol Int. Volume: 69 Issue: 5 Pages: 249-259
  • DOI: 10.1111/pin.12798
  • NAID: 120006732053
  • Peer Reviewed
• [Presentation] 肺腺癌における癌関連タンパク質CD109 の機能解析 (2019)
  • Author(s): 滝哲郎、三井伸二、白木之浩、榎本篤、高橋雅英
  • Organizer: 第108 回日本病理学会総会
• [Presentation] 骨組織および骨肉腫におけるGPI アンカー型膜タンパク質CD109 の発 現とその意義 (2019)
  • Author(s): 三井伸二、白木之浩、下山芳江、榎本篤、高橋雅英
  • Organizer: 第108 回日本病理学会総会
• [Presentation] 肺腺癌におけるGPIアンカー型膜タンパク質CD109の機能解析 (2019)
  • Author(s): 滝 哲郎、三井 伸二、白木 之浩、榎本 篤、高橋 雅英
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] Expression and clinical role of a glycosylphosphatidylinositol-anchored protein CD109 in non-squamous cell tumors (2018)
  • Author(s): Shinji Mii，Yukihiro Shiraki，Tetsuro Taki，Atsushi Enomoto，Naoya Asai，Masahide Takahashi
  • Organizer: 第64回日本病理学会秋期特別総会
• [Presentation] The role of CD109 in Brain tumor stem cells derived from PDGFB-induced glioma mouse model (2018)
  • Author(s): Yukihiro Shiraki, Shinji Mii, Naoya Asai, Atsushi Enomoto, Masahide Takahashi
  • Organizer: 第107回日本病理学会総会
• [Presentation] Dissection of the function of CD109 in lung adenocarcinoma (2018)
  • Author(s): 三井 伸二、白木 之浩、榎本 篤、高橋 雅英
  • Organizer: 第77回日本癌学会学術総会