Role of tumor-derived semaphorin 3A in the development of cancer pain

• Project/Area Number: 15K08682
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Nigata University of Phermacy and Applied Life Sciences
• Principal Investigator: Maeda Takehiko 新潟薬科大学, 薬学部, 教授 (50271010)
• Co-Investigator(Kenkyū-buntansha): 山田 大祐 新潟薬科大学, 薬学部, 助手 (50733680) ; 川原 浩一 新潟薬科大学, 薬学部, 准教授 (10347015)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: セマフォリン3A / がん性疼痛 / mTOR / がん幹細胞 / 薬剤抵抗性 / セマフォリン / miRNA / 腫瘍細胞 / 骨転移腫瘍 / 骨痛 / 骨芽細胞

Outline of Final Research Achievements

Elucidation of potential therapeutic targets for bone cancer pain would contribute to relief of the intractable and unbearable pain. We used microarray analysis to reveal upregulation of semaphorin 3A (Sema3A) in the model mice for bone cancer pain. Knockdown of Sema3A and inhibition of Sema3A cellular signaling attenuated the tumor growth and the development of the pain. These results suggest that Sema3A is a potential therapeutic target molecule for the development of bone cancer pain.

Research Products

• [Journal Article] Synthesis and evaluation of radioiodinated 1-{2-[5-(2-methoxyethoxy)-1 H -benzo[ d ]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging (2017)
  • Author(s): Effendi Nurmaya、Ogawa Kazuma、Mishiro Kenji、Takarada Takeshi、Yamada Daisuke、Kitamura Yoji、Shiba Kazuhiro、Maeda Takehiko、Odani Akira
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 25 Issue: 20 Pages: 5576-5585
  • DOI: 10.1016/j.bmc.2017.08.025
  • NAID: 120006375101
  • Peer Reviewed
• [Journal Article] Autocrine Semaphorin3A signaling is essential for the maintenance of stem-like cells in lung cancer. (2016)
  • Author(s): Yamada D, Takahashi K, Kawahara K, Maeda T.
  • Journal Title: Biochem Biophys Res Commun Volume: 480 Issue: 3 Pages: 375-379
  • DOI: 10.1016/j.bbrc.2016.10.057
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Plexin A1 signaling confers malignant phenotypes in lung cancer cells. (2016)
  • Author(s): Yamada D, Watanabe S, Kawahara K, Maeda T.
  • Journal Title: Biochem Biophys Res Commun Volume: 480 Issue: 1 Pages: 75-80
  • DOI: 10.1016/j.bbrc.2016.10.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling. (2016)
  • Author(s): Yamada D, Kawahara K, Maeda T.
  • Journal Title: Biochem Biophys Res Commun Volume: 476 Issue: 4 Pages: 475-480
  • DOI: 10.1016/j.bbrc.2016.05.147
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cancer pain relief achieved by disrupting tumor-driven semaphorin 3A signaling in mice. (2016)
  • Author(s): Maeda T, Yamada D, Kawahara K.
  • Journal Title: Neurosci Lett Volume: 632 Pages: 147-151
  • DOI: 10.1016/j.neulet.2016.08.060
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB/osteoactivin processed by furin-like protease(s) in a subpopulation of microglia in neonatal rat brain. (2016)
  • Author(s): Kawahara K, Hirata H, Ohbuchi K, Nishi K, Maeda A, Kuniyasu A, Yamada D, Maeda T, Tsuji A, Sawada M, Nakayama H.
  • Journal Title: Glia Volume: 64 Issue: 11 Pages: 1938-1961
  • DOI: 10.1002/glia.23034
  • NAID: 120006510950
  • Peer Reviewed / Open Access
• [Journal Article] Tumor cell-derived secretory factor downregulates Semaphorin-3a in osteoblasts by activating mammalian target of rapamycin pathway (2016)
  • Author(s): Yamada D, Kawahara K, Ozaki M, Maeda T
  • Journal Title: Biosci Biotechnol Biochem Volume: 80 Issue: 5 Pages: 942-944
  • DOI: 10.1080/09168451.2015.1136881
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] セマフォリン6Bは肺がん幹細胞の維持に関与する (2017)
  • Author(s): 山田大祐、前田武彦
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 自己分泌型セマフォリン3aシグナルによる骨転移腫瘍の発症制御機構 (2016)
  • Author(s): 山田大祐、川原浩一、前田武彦
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] 癌性疼痛下のモルヒネ報酬効果減弱におけるミクログリアの機能的関与 (2016)
  • Author(s): 前田武彦、山田大祐、川原浩一、池田崇志、丸山光、塚本敬、五十嵐悠亮、中沢美穂
  • Organizer: 第67回日本薬理学会北部会
  • Place of Presentation: 札幌
• [Presentation] がん疼痛下のモルヒネ報酬効果減弱におけるミクログリアの関与 (2016)
  • Author(s): 前田武彦、池田崇志、丸山光、塚本敬、五十嵐悠亮、山田大祐、川原浩一
  • Organizer: 第36回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 札幌
• [Presentation] がん疼痛形成のセマフォリン3aによる制御機構 (2016)
  • Author(s): 前田武彦、山田大祐、川原浩一
  • Organizer: 生体機能と創薬シンポジウム2016
  • Place of Presentation: 仙台
  • Invited
• [Presentation] がん疼痛モデルの特性とがん分子機構の研究 (2015)
  • Author(s): 前田武彦
  • Organizer: 第9回日本緩和医療薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2015-10-02
  • Invited
• [Presentation] 骨がん性疼痛モデルマウスの特性とオキシコドンの効果 (2015)
  • Author(s): 前田武彦、丸山恵奈、柳 真美、山岸 明、山田大祐、川原浩一
  • Organizer: 第66回日本薬理学会北部会
  • Place of Presentation: 富山
  • Year and Date: 2015-09-18