The elucidation of the molecular mechanism underlying homeostasis against cancer

• Project/Area Number: 18K15246
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kumamoto University
• Principal Investigator: Horiguchi Haruki 熊本大学, 生命資源研究・支援センター, 特任助教 (70755454)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: がん免疫 / 大腸がん / アンジオポエチン様因子2 / 恒常性維持機構 / 腸管免疫 / 腫瘍免疫

Outline of Final Research Achievements

We conducted mechanistic analysis comparing ANGPTL2 function in cancer progression in a murine syngeneic model. ANGPTL2 deficiency accelerated tumor progression, supporting a tumor-suppressing role. Moreover, host ANGPTL2 facilitates CD8+ T-cell cross-priming and enhances anti-tumor immune responses. Importantly, ANGPTL2 activates dendritic cells and enhances tumor vaccine efficacy.

Academic Significance and Societal Importance of the Research Achievements

腫瘍細胞の小さな集団が発生しても、効果的な免疫反応を惹起し、腫瘍が退縮する可能性が提唱されてから、これまでがん免疫研究が盛んに行われており、免疫によるがん治療は今世界中で注目されている。しかしながら、免疫とがんの発症・進展の関連は十分には解明されていない。本研究では、がん免疫応答を促進する新たな分子としてANGPTL2の機能を解明した。抗腫瘍免疫の分子メカニズムについて理解することが、がんの予防および新規治療法開発に向けた研究の基盤となる。

Research Products

• [Journal Article] Tumor cell-derived angiopoietin-like protein 2 establishes a preference for glycolytic metabolism in lung cancer cells. (2020)
  • Author(s): Osumi H, Horiguchi H, Kadomatsu T, Tashiro K, Morinaga J, Takahashi T, Ikeda K, Ito T, Suzuki M, Endo M, Oike Y
  • Journal Title: Cancer Sci Volume: - Issue: 4 Pages: 1241-1253
  • DOI: 10.1111/cas.14337
  • Peer Reviewed / Open Access
• [Journal Article] Loss of Endogenous HMGB2 Promotes Cardiac Dysfunction and Pressure Overload-Induced Heart Failure in Mice (2019)
  • Author(s): Sato M, Miyata K, Tian Z, Kadomatsu T, Ujihara Y, Morinaga J, Horiguchi H, Endo M, Zhao J, Zhu S, Sugizaki T, Igata K, Muramatsu M, Minami T, Ito T, Bianchi ME, Mohri S, Araki K, Node K, Oike Y
  • Journal Title: Circulation Journal Volume: 83 Issue: 2 Pages: 368-378
  • DOI: 10.1253/circj.CJ-18-0925
  • NAID: 130007557092
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-01-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity. (2019)
  • Author(s): Horiguchi H, Kadomatsu T, Kurahashi R, Hara C, Miyata K, Baba M, Osumi H, Terada K, Araki K, Takai T, Kamba T, Linehan WM, Moroishi T, Oike Y.
  • Journal Title: Genes Dev Volume: 33 Issue: 23-24 Pages: 1641-1656
  • DOI: 10.1101/gad.329417.119
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of circulating ANGPTL 3, 4, and 8 levels with medical status in a population undergoing routine medical checkups: A cross-sectional study. (2018)
  • Author(s): Morinaga J, Zhao J, Endo M, Kadomatsu T, Miyata K, Sugizaki T, Okadome Y, Tian Z, Horiguchi H, Miyashita K, Maruyama N, Mukoyama M, Oike Y.
  • Journal Title: PLoS One Volume: 13 Issue: 3 Pages: e0193731-e0193731
  • DOI: 10.1371/journal.pone.0193731
  • Peer Reviewed / Open Access