Expression analysis of tumor-associated macrophages and application of treatment for colorectal cancer

• Project/Area Number: 17K09374
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: Inagaki Satoko 金沢大学, 附属病院, 医員 (00768781)
• Co-Investigator(Kenkyū-buntansha): 久保田 英嗣 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (30405188) ; 澤田 武 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (60345626)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 大腸癌 / 腫瘍関連マクロファージ / 遺伝子変異 / 個別化治療 / 下部消化管学（小腸、大腸）

Outline of Final Research Achievements

The aim of this study was to clarify the involvement of tumor-associated macrophages (TAM) in the microenvironment of colorectal cancer by analyzing these expression profiles. However, dissociation of TAM from colorectal cancer tissue was unsuccessful. Instead, protein expression study was performed in advanced colorectal cancer and colorectal premalignant lesions by immunohistochemistry. However, association between invasion of TAM and clinicopathological factors was not shown. Alternatively, the prevalence of abnormal nuclear β-catenin accumulation was shown to be significantly higher in traditional serrated adenomas (TSAs) than sessile serrated adenomas by immunohistochemistry, indicating the significance of Wnt signaling pathway activation in the carcinogenesis of TSAs.

Academic Significance and Societal Importance of the Research Achievements

当初の目的である、腫瘍関連マクロファージの大腸癌の増殖、浸潤に果たす役割の解明を果たすことはできなかった。しかし、副次的に、大腸鋸歯状腺腫において高頻度にβカテニンの核内集積が確認され、Wntシグナル経路の亢進が発癌に寄与している可能性が示された。本研究の結果から、従来提唱されてきた管状腺腫、無茎性鋸歯状腺腫を前癌病変とする発癌経路とは異なる第3の大腸発癌経路の存在が示された。本研究の結果は、大腸鋸歯状腺腫を前癌病変とする大腸癌に対する、Wntシグナル経路を標的とした新たな分子標的治療の開発に資することができると考えられる。

Research Products

• [Journal Article] Significance of gene mutations in the Wnt signaling pathway in traditional serrated adenomas of the colon and rectum (2020)
  • Author(s): Nakanishi, H. Sawada, T. Kaizaki, Y. Ota, R. Suzuki, H. Yamamoto, E. Aoki, H. Eizuka, M. Hasatani, K. Takahashi, N. Inagaki, S. Ebi, M. Kato, H. Kubota, E. Kataoka, H. Takahashi, S. Tokino, T. Minamoto, T. Sugai, T. Sasaki, Y.
  • Journal Title: PLoS One Volume: 15 Issue: 2 Pages: e0229262-e0229262
  • DOI: 10.1371/journal.pone.0229262
  • Peer Reviewed / Open Access