Investigation of mechanisms of Wnt signal on prostate and trial to develop the new treatment of metastatic Castration Resistant Prostate Cancer

• Project/Area Number: 26861259
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: The University of Tokyo
• Principal Investigator: TAKAHASHI SAYURI 東京大学, 医学部附属病院, 講師 (40313217)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 前立腺癌 / Wntシグナル / Wnt / Androgen Receptro / Prostate cancer / Ｗｎｔシグナル / バイオマーカー

Outline of Final Research Achievements

We compared the mRNA expression levels of non-canonical Wnts of formalin-fixed, paraffin-embedded (FFPE) samples from radical prostatectomy patients. mRNA levels of Wnt5B were associated with GS by quantitative-PCR. we knock-downed RNA expression of Wnt5B of prostate cancer cells and found the gene expression of growth factors reduced. Wnt5B promoted proliferation and invasion of PC3 cells by MTT and invasion assay. We preserved serum samples of 112 patients at our out clinic for the follow-up. We measured serum Wnt5B levels by ELISA. 59 patients were diagnosed as metastatic prostate cancer and 53 patients were not found any metastases. Serum Wnt5B levels of metastases group were significantly higher than those of non-metastases group. This result suggests that increasing serum Wnt5B strongly associated with increased risk of metastases of prostate cancer. Wnt5B may be a novel target for treatment of metastatic prostate cancer.

Research Products

• [Journal Article] Nanowire analysis of cancer-testis antigens as biomarkers of aggressive prostate cancer. (2015)
  • Author(s): Takahashi S, Shiraishi T, Miles N, Trock BJ, Kulkarni P, Getzenberg RH.
  • Journal Title: Urology Volume: 85(3) Issue: 3 Pages: 704.e1-704.e7
  • DOI: 10.1016/j.urology.2014.12.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Urinary oxalate excretion decreased in androgen receptor-knockout mice by suppressing oxalate synthesis in the liver (2015)
  • Author(s): Takahashi Sayuri, Aruga Seiji, Yamamoto Yoko, Takahiro Matsumoto, Kitamura Tadaichi and Homma Yukio
  • Journal Title: Open Journal of Urology Volume: 450 Issue: 08 Pages: 123-132
  • DOI: 10.4236/oju.2015.58020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Clinical Application of Serum Wnt5B as Novel Biomarker of Metastatic Castration Resistant Prostate Cancer (2017)
  • Author(s): 高橋さゆり
  • Organizer: 第105回日本泌尿器科学会総会総会賞ポスター
  • Place of Presentation: 鹿児島
  • Year and Date: 2017-04-21
• [Presentation] Non-canonical Wntシグナルと前立腺癌悪性度の関連性の検討 (2017)
  • Author(s): 高橋さゆり
  • Organizer: 第26回泌尿器分子細胞研究会
  • Place of Presentation: 大分
  • Year and Date: 2017-03-10
• [Presentation] 骨転移性前立腺癌におけるNon-canonical Wntシグナルを軸とする骨微小環境の分子ネットワークの解明 (2016)
  • Author(s): 高橋さゆり
  • Organizer: 第32回前立腺シンポジウム
  • Place of Presentation: 品川
  • Year and Date: 2016-12-10
  • Invited
• [Presentation] The Role of Androgen Receptor and Microenvironment of Prostate Cancer (2015)
  • Author(s): 高橋さゆり
  • Organizer: PCS World Congress of Urology2015
  • Place of Presentation: Warsaw, Poland
  • Year and Date: 2015-10-30
  • Int'l Joint Research / Invited
• [Presentation] Androgen receptor positive stromal cells regulate prostate cancer proliferation through non-canonical Wnt signaling (2015)
  • Author(s): Sayuri Takahashi
  • Organizer: AUA
  • Place of Presentation: USA
  • Year and Date: 2015-05-15 – 2015-05-19
• [Presentation] Androgen receptor positive stromal cells regulate prostate cancer proliferation through non-canonical Wnt Signaling (2015)
  • Author(s): 高橋さゆり
  • Organizer: AUA Annual Meeting
  • Place of Presentation: New Orleans,TX, USA
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] Wntシグナルを利用した前立腺癌骨転移に対する新規治療標的薬とバイオマーカーの探索 (2015)
  • Author(s): 高橋さゆり
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18 – 2015-04-21
• [Presentation] The Role of Androgen Receptor and Microenvironment of Prostate Cancer (2015)
  • Author(s): 高橋さゆり
  • Organizer: 第103回日本泌尿器科学会総会 若手フロンティアシンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18 – 2015-04-21
• [Presentation] The Role of Androgen Receptor and Microenvironment of Prostate Cancer (2015)
  • Author(s): 高橋さゆり
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18
• [Presentation] 第8回ヤングリサーチグラント受賞者講演「Wntシグナルを利用した前立腺癌骨転移に対する新規治療標的とバイオマーカーの探索」 (2015)
  • Author(s): 高橋さゆり
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18
  • Invited
• [Presentation] Androgen receptor positive stromal cells regulate prostate cancer proliferation through non-canonical Wnt signaling (2015)
  • Author(s): Sayuri Takahashi
  • Organizer: EUA2015
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2015-03-20 – 2015-03-24
• [Presentation] 前立腺癌：細胞間相互作用 (2014)
  • Author(s): 高橋さゆり
  • Organizer: 第4回前立腺生物学シンポジウム伊勢志摩2014
  • Place of Presentation: 伊勢志摩
  • Year and Date: 2014-06-26 – 2014-06-27
• [Book] 「がん」「次世代のがん治療薬・診断のための研究開発」 (2015)
  • Author(s): 高橋さゆり他
  • Total Pages: 399
  • Publisher: 技術情報協会株式会社