Early detection and secondary prevention of cancers using a molecular target

• Project/Area Number: 16K07141
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kibi International University (2018); Kyoto University (2016-2017)
• Principal Investigator: Takahashi Atsushi 吉備国際大学, 保健医療福祉学部, 教授 (80303840)
• Research Collaborator: LI yan
• Project Period (FY): 2016-10-21 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 癌予防 / 癌早期発見 / 遺伝子改変マウス / METTL13 / ライディッヒ細胞 / 停留精巣 / 癌 / 予防医学 / 生物・生体工学

Outline of Final Research Achievements

FEAT tumor promoter, encoded by the METTL13 gene, is overexpressed in most human cancers and circulates in the bloodstream of cancer patients. We explored the possibility of applying FEAT expression to early diagnostics and secondary cancer prevention strategies. We did not succeed in producing conditional FEAT knockout mice using ordinary ES cells. However, RENKA ES cells of TransGenic Inc. have enabled us to obtain Mettl13(flox/+) mice. We also found that FEAT inhibits primary cilia formation, facilitates INSL3 production, and supports transabdominal testis migration in vivo.

Academic Significance and Societal Importance of the Research Achievements

1970年代以来の癌関連遺伝子の研究は、癌の診断や治療のみならず、正常組織の機能を分子レベルで明らかにすることにも役立って来た。停留精巣（停留睾丸）は、新生児の先天異常の中で最も頻度が高く、精子形成不全、不妊症の原因となり、悪性腫瘍（癌）の母地となる。しかし、その分子機構はほとんどわかっていない。当研究は腫瘍促進因子FEATの研究から、停留精巣の分子機構に光を当て、小児の健康に貢献するものである。

Research Products

• [Journal Article] FEAT enhances INSL3 expression in testicular Leydig cells. (2018)
  • Author(s): Li Y, Kobayashi K, Murayama K, Kawahara K, Shima Y, Suzuki A, Tani K, *Takahashi A.
  • Journal Title: Genes Cells Volume: 23 Issue: 11 Pages: 952-962
  • DOI: 10.1111/gtc.12644
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A phase I clinical trial of RNF43 peptide-related immune cell therapy combined with low-dose cyclophosphamide in patients with advanced solid tumors. (2018)
  • Author(s): Hijikata Y, Okazaki T, Tanaka Y, Murahashi M, Yamada Y, Yamada K, Takahashi A, Inoue H, Kishimoto J, Nakanishi Y, Oda Y, Nakamura Y, Tani K
  • Journal Title: PLoS One Volume: 13 Issue: 1 Pages: e0187878-e0187878
  • DOI: 10.1371/journal.pone.0187878
  • Peer Reviewed / Open Access
• [Journal Article] 分子標的を用いた網羅的癌早期発見 (2018)
  • Author(s): 高橋 淳
  • Journal Title: 実験医学 Volume: 36 Pages: 3106-3106
• [Journal Article] Therapeutic vaccination based on side population cells transduced by the granulocyte-macrophage colony-stimulating factor gene elicits potent antitumor immunity. (2017)
  • Author(s): Sakamoto C, Kohara H, Inoue H, Narusawa M, Ogawa Y, Hirose-Yotsuya L, Miyamoto S, Matsumura Y, Yamada K, Takahashi A, Tani K
  • Journal Title: Cancer Gene Ther. Volume: 24 Issue: 4 Pages: 165-174
  • DOI: 10.1038/cgt.2016.80
  • Peer Reviewed
• [Journal Article] Immunogenic FEAT protein circulates in the bloodstream of cancer patients (2016)
  • Author(s): Li Y, Kobayashi K, Mona MM, Satomi C, Okano S, Inoue H, Tani K, Takahashi A
  • Journal Title: J. Transl. Med. Volume: 14 Issue: 1 Pages: 275-275
  • DOI: 10.1186/s12967-016-1034-2
  • NAID: 120006345015
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phase I clinical trial of a five-peptide vaccine combined with cyclophosphamide in advanced solid tumors. (2016)
  • Author(s): Murahashi, M., Hijikata, Y., Yamada, K., Tanaka, Y., Kishimoto, J., Inoue, H., Marumoto, T., Takahazhi, A., Okazaki, T., Takeda, K., Hirakawa, M., Fujii, H., Okano, S., Morita, M., Baba, E., Mizumoto, K., Maehara, Y., Tanaka, M., Akashi, K., Nakanishi, Y., Yoshida, K., Tsunoda, T., Tamura, K., Nakamura, Y., & Tani, K.
  • Journal Title: Clin. Immunol. Volume: 166-167 Pages: 48-58
  • DOI: 10.1016/j.clim.2016.03.015
  • Peer Reviewed
• [Presentation] FEAT downregulates primary cilia formation and enhances INSL3 expression in testicular Leydig cells (2018)
  • Author(s): Y. Li, A. Takahashi
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] 腫瘍促進因子FEATの免疫原性の検討と癌患者血漿での検出 (2018)
  • Author(s): Y. Li, A. Takahashi
  • Organizer: 第76回日本癌学会学術総会