Impact of immune cell infiltration by microbiome and fat inflammation on HFD induced prostate cancer progression

• Project/Area Number: 19K09663
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Akita University
• Principal Investigator: Narita Shintaro 秋田大学, 医学系研究科, 准教授 (40396552)
• Co-Investigator(Kenkyū-buntansha): 井上 高光 国際医療福祉大学, 国際医療福祉大学成田病院, 教授 (60375243) ; 齋藤 満 秋田大学, 医学部附属病院, 准教授 (80400505)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 前立腺癌 / 脂質 / 腸内細菌 / 高脂肪食 / 制御性T細胞

Outline of Research at the Start

前立腺癌マウスモデルを用いて動物性脂肪摂取による癌増悪・進展に腸内細菌叢、脂肪組織炎症、血清サイトカイン変化、癌周囲免疫担当細胞浸潤が関連するかを検討し、得られた知見をマウスモデル、細胞実験およびヒト検体を用いvalidationする。癌増殖に対する腸内細菌の関与や、有望な関連分子が同定できたら再びマウスモデルを用いて、癌治療効果を検討する。①動物モデルによる仮説検討②動物モデル、細胞実験、臨床検体による検証③動物モデルによる治療効果確認の3部構成である。

Outline of Final Research Achievements

We assess the relationship among diet, gut microbiota, lipid metabolism and immune microenvironment during diet induced prostate cancer progression. We found that saturated and/or mono-unsaturated fatty acid promotes prostate cancer progression with alteration of orders Clostridales and Lactobacillales and modulation of cholesterol/lipid metabolism in prostate tumors.

Academic Significance and Societal Importance of the Research Achievements

特定の脂質摂取の前立腺癌増悪・進展への分子生物学的関係性が明らかになると、これまで同定されていなかった新規の前立腺癌治療標的発見の足掛かりになるのみならず、食事や肥満といった生活因子や腸内細菌変動による癌治療や癌予防戦略につながる可能性があると考えている。

Research Products

• [Journal Article] pecific Gut Microbial Environment in Lard Diet-Induced Prostate Cancer Development and Progression. (2022)
  • Author(s): Sato H, Narita S, Ishida M, Takahashi Y, Mingguo H, Kashima S, Yamamoto R, Koizumi A, Nara T, Numakura K, Saito M, Yoshioka T, Habuchi T.
  • Journal Title: Int J Mol Sci. Volume: 23 Issue: 4 Pages: 2214-2214
  • DOI: 10.3390/ijms23042214
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Nuclear YAP1 Expression in Residual Cancer After Neoadjuvant Chemohormonal Therapy With Docetaxel for High-Risk Localized Prostate Cancer (2020)
  • Author(s): Yoshinori Matsuda, Shintaro Narita, Taketoshi Nara, Huang Mingguo, Hiromi Sato, Atsushi Koizumi, Sohei Kanda, Kazuyuki Numakura, Mitsuru Saito, Takamitsu Inoue, Yuko Hiroshima, Hiroshi Nanji, Shigeru Satoh, Norihiko Tsuchiya, Tomonori Habuchi
  • Journal Title: BMC Cancer Volume: 20 Issue: 1 Pages: 2034-2034
  • DOI: 10.1186/s12885-020-06844-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased fatty acyl saturation of phosphatidylinositol phosphates in prostate cancer progression (2019)
  • Author(s): Koizumi Atsushi、Narita Shintaro、Nakanishi Hiroki、Ishikawa Masaki、Eguchi Satoshi、Kimura Hirotaka、Takasuga Shunsuke、Huang Mingguo、Inoue Takamitsu、Sasaki Junko、Yoshioka Toshiaki、Habuchi Tomonori、Sasaki Takehiko
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 13257-13257
  • DOI: 10.1038/s41598-019-49744-3
  • Peer Reviewed / Open Access
• [Journal Article] Research Evidence on High-Fat Diet-Induced Prostate Cancer Development and Progression (2019)
  • Author(s): Narita S, Nara T, Sato H, et al.
  • Journal Title: J Clin Med. Volume: 8 Issue: 5 Pages: 597-597
  • DOI: 10.3390/jcm8050597
  • Peer Reviewed / Open Access
• [Presentation] Cellular retinoic acid-binding protein 2 enhances saturated fatty acid-induced prostate cancer progression. (2021)
  • Author(s): Hiromi, Sato., Shintaro, Narita., Masanori, Ishida., Soki, Kashima., Ryohei, Yamamoto., Atsuishi, Koizumi., Taketoshi, Nara., Kazuyuki, Numakura., Mitsuru, Saito., Shigeru, Satoh., Naoshi, Dohmae., Tomonori, Habuchi
  • Organizer: AACR Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] Lard diet accelerates prostate cancer development with modulation of systematic and local inflammation and gut microbiota alteration in a Pten-deficient mouse model. (2021)
  • Author(s): Hiromi, Sato., Shintaro, Narita., Ryohei, Yamamoto., Atsuishi, Koizumi., Taketoshi, Nara., Mingguo, Huang., Kazuyuki, Numakura., Mitsuru, Saito., Naoshi, Dohmae., Tosiaki, Yoshioka., Tomonori, Habuchi
  • Organizer: The 36th Annual EAU congress
  • Int'l Joint Research
• [Presentation] Cellular retinoic acid-binding protein 2 (CRABP2) enhances saturated fatty acid-induced prostate cancer progression. (2021)
  • Author(s): Hiromi, Sato., Shintaro, Narita., Masanori, Ishida., Soki, Kashima., Ryohei, Yamamoto., Atsuishi, Koizumi., Taketoshi, Nara., Mingguo, Huang., Kazuyuki, Numakura., Mitsuru, Saito., Naoshi, Dohmae., Tomonori, Habuchi
  • Organizer: 第80回日本癌学会総会
• [Presentation] 2種の免疫応答性マウスモデルにおける飽和脂肪酸の前立腺癌発症・進展に対する影響 (2021)
  • Author(s): 佐藤博美, 成田伸太郎, 石田雅宣, 山本竜平, 小泉淳, 奈良健平, 沼倉一幸, 齋藤満, 佐藤滋, 吉岡年明, 羽渕友
  • Organizer: 第110回日本泌尿器科学会総会
• [Presentation] Fish -oil diet attenuates prostate cancer development with systematic inflammation protection and gut microbiota alteration in a Pten-deficient mouse model. (2020)
  • Author(s): Hiromi, Sato., Shintaro, Narita., Mitsuru, Saito., Ryohei, Yamamoto., Atsuishi, Koizumi., Taketoshi, Nara., Sohei, Kanda., Kazuyuki, Numakura., Takamitsu, Inoue., Shigeru, Satoh., Kyoko, Abe., Tomonori, Habuchi
  • Organizer: The 115th Annual Meeting of the American Urological Association
  • Int'l Joint Research
• [Presentation] The impact of specific fat-diets and obesity on prostate cancer initiation and progression using two different immunocompetent mouse models (2020)
  • Author(s): Hiromi, Sato., Shintaro, Narita., Ryohei, Yamamoto., Atsuishi, Koizumi., Taketoshi, Nara., Kazuyuki, Numakura., Mitsuru, Saito., Takamitsu, Inoue., Shigeru, Satoh., Tosiaki, Yoshioka., Tomonori, Habuchi
  • Organizer: The 35th Annual EAU congress
  • Int'l Joint Research
• [Presentation] PTENノックアウト前立腺癌マウスモデルにおいてラード食は全身炎症と腸内細菌叢の変化を介して前立腺癌進展を促進する (2020)
  • Author(s): 佐藤博美, 成田伸太郎, 山本竜平, 小泉淳, 奈良健平, 神田壮平, 沼倉一幸, 齋藤満, 井上高光, 佐藤滋, 吉岡年明, 羽渕友則
  • Organizer: 第24回腸内細菌学会
• [Presentation] 2種の免疫応答性マウスモデルにおける特定の脂肪食が前立腺癌発症・進展に及ぼす影響 (2020)
  • Author(s): 佐藤博美, 成田伸太郎, 山本竜平, 小泉淳, 奈良健平, 神田壮平, 沼倉一幸, 齋藤満, 井上高光, 佐藤滋, 吉岡年明, 羽渕友則
  • Organizer: 第79回日本癌学会
• [Presentation] Impact of positive surgical margin and nerve-sparing status on biochemical recurrence in patients with prostate cancer treated with radical prostatectomy: a multicenter retrospective study. (2019)
  • Author(s): Shintaro Narita, Yoshinori Matsuda, Atsushi Koizumi, et al.
  • Organizer: The 114th Annual Meeting of the American Urological Association,
  • Int'l Joint Research
• [Presentation] Acute kidney injury and its impact on renal prognosis following robot-assisted laparoscopic radical prostatectomy. (2019)
  • Author(s): Shintaro Narita, Hiromi Sato, Atsushi Koizumi, et al.
  • Organizer: The 36th Korea-Japan Urological Congress 2019
  • Int'l Joint Research
• [Presentation] The expression profile of phosphatidylinositol phosphates in clinical renal cell carcinoma. (2019)
  • Author(s): Shintaro Narita, Hiroki Nakanishi, Yoshinori Matsuda, et al.
  • Organizer: 第78回日本癌学会総会
• [Presentation] Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy (2019)
  • Author(s): Shintaro Narita, Kyoko Nomura, Shingo Hatakeyama, et al.
  • Organizer: 第57回日本癌治療学会学術総会