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Development of novel cancer metastasis suppressing agent focusing on cell adhesion controling

Research Project

Project/Area Number 20K09905
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionHiroshima University

Principal Investigator

Asano Satoshi  広島大学, 医系科学研究科(歯), 助教 (30570535)

Co-Investigator(Kenkyū-buntansha) 兼松 隆  九州大学, 歯学研究院, 教授 (10264053)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords乳癌 / 細胞増殖 / 細胞遊走 / VIP / Gαs / VIPR2 / PI3キナーゼ / Gαi / ERK / PI3K / イノシトールリン脂質 / アクチン / VPAC2 / 糸状仮足 / 細胞移動 / 遊走 / 細胞接着 / 転移
Outline of Research at the Start

癌細胞の移動のし易さは、癌の転移能と密接に関わっている。細胞が移動するためには、接着力の強弱が時空間的に適切に制御される必要がある。我々はPLC-related catalytically inactive protein (PRIP) が新規の細胞接着調節タンパク質であることを見出した(未発表研究)。そして、PRIPの過剰発現癌細胞株を用いたマウス転移モデルの実験の結果、PRIPが癌細胞の増殖や転移を負に制御していることを明らかにした。本研究では、PRIPによる細胞接着の調節メカニズムを明らかにし、その知見を癌細胞の細胞移動、転移制御に応用することによって、新しい転移抑制剤の開発を目指す。

Outline of Final Research Achievements

We investigated whether vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is involved in exacerbation (cell migration and proliferation) of breast cancer. We demonstrated that stable expression of VIPR2 in breast cancer cells promoted VIP-induced cell migration and cell proliferation, and enhanced the proliferation in intraperitoneal in vivo. In contrast, treatment with the VIPR2-selective antagonist peptide KS-133 abolished the effects of VIPR2 overexpression and markedly inhibited VIP-induced cell migration and proliferation. These results indicate that VIPR2 signaling regulates breast cancer cell migration and proliferation, and suggest that disruption of this signaling by VIPR2 overexpression may lead to exacerbation of breast cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究は、脳神経細胞の解析から研究代表者らが見いだした神経突起伸長に関わる新規シグナルVIP-VIPR2を癌細胞研究へと応用した、学術的意義の大きいものであり、その達成は、生体で利用可能な新規抗癌剤の開発に繋がるものである。VIPR2は全身にわたる諸臓器で発現しており、それらの臓器を原発部位とする癌細胞でVIPR2遺伝子の変異やコピー数の増加が高頻度に観察されているという大きな特色がある。またVIPR2はGタンパク質共役型受容体であり、創薬標的としての妥当性が高く、治療薬開発の実現に向けて大きな可能性を秘めている。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (39 results)

All 2023 2022 2021 2020

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 10 results) Presentation (26 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Development of the vasoactive intestinal peptide receptor 2 (VIPR2) antagonist peptide for the treatment of schizophrenia2023

    • Author(s)
      Ago Yukio、Asano Satoshi、Sakamoto Kotaro
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 158 Issue: 3 Pages: 242-245

    • DOI

      10.1254/fpj.22146

    • ISSN
      0015-5691, 1347-8397
    • Year and Date
      2023-05-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vasoactive intestinal peptide receptor 2 signaling promotes breast cancer cell proliferation by enhancing the ERK pathway2023

    • Author(s)
      Asano Satoshi、Ono Ami、Sakamoto Kotaro、Hayata-Takano Atsuko、Nakazawa Takanobu、Tanimoto Kotaro、Hashimoto Hitoshi、Ago Yukio
    • Journal Title

      Peptides

      Volume: 161 Pages: 170940-170940

    • DOI

      10.1016/j.peptides.2023.170940

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of the monoaminergic system in the antidepressant effects of ketamine and its metabolites2023

    • Author(s)
      Ago Y, Yokoyama R, Asano S, Hashimoto H
    • Journal Title

      Neuropharmacology

      Volume: 223 Pages: 109313-109313

    • DOI

      10.1016/j.neuropharm.2022.109313

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new method for assessing depressive-like behaviors in female mice2023

    • Author(s)
      吾郷由希夫, 浅野智志
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 158 Issue: 1 Pages: 35-38

    • DOI

      10.1254/fpj.22101

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imipramine prevents Porphyromonas gingivalis lipopolysaccharide-induced microglial neurotoxicity2022

    • Author(s)
      Yamawaki Yosuke、So Hiroki、Oue Kana、Asano Satoshi、Furusho Hisako、Miyauchi Mutsumi、Tanimoto Kotaro、Kanematsu Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 634 Pages: 92-99

    • DOI

      10.1016/j.bbrc.2022.09.109

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] AlphaFold version 2.0 elucidates the binding mechanism between VIPR2 and KS-133, and reveals an S-S bond (Cys25-Cys192) formation of functional significance for VIPR22022

    • Author(s)
      Sakamoto K, Asano S, Ago Y, Hirokawa T
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 636 Pages: 10-16

    • DOI

      10.1016/j.bbrc.2022.10.071

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation2022

    • Author(s)
      Imado E, Sun S, Abawa AR, Tahara T, Kochi T, Huynh TNB, Asano S, Hasebe S, Nakamura Y, Hisaoka-Nakashima K, Kotake Y, Irifune M, Tsuga K, Takuma K, Morioka N, Kiguchi N, Ago Y.
    • Journal Title

      Neurochemistry International

      Volume: 160 Pages: 105415-105415

    • DOI

      10.1016/j.neuint.2022.105415

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vasoactive intestinal peptide?VIPR2 signaling regulates tumor cell migration2022

    • Author(s)
      Asano Satoshi、Yamasaka Misa、Ozasa Kairi、Sakamoto Kotaro、Hayata-Takano Atsuko、Nakazawa Takanobu、Hashimoto Hitoshi、Waschek James A.、Ago Yukio
    • Journal Title

      Frontiers in Oncology

      Volume: 12 Pages: 852358-852358

    • DOI

      10.3389/fonc.2022.852358

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phospholipase C-related catalytically inactive protein enhances cisplatin-induced apoptotic cell death2022

    • Author(s)
      Asano Satoshi、Maetani Yuka、Ago Yukio、Kanematsu Takashi
    • Journal Title

      European Journal of Pharmacology

      Volume: 933 Pages: 175273-175273

    • DOI

      10.1016/j.ejphar.2022.175273

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of PRIP, a phosphatidylinositol 4,5-bisphosphate binding protein, attenuates PI3K/AKT signaling and suppresses tumor growth in a xenograft mouse model2021

    • Author(s)
      Maetani Yuka、Asano Satoshi、Mizokami Akiko、Yamawaki Yosuke、Sano Tomomi、Hirata Masato、Irifune Masahiro、Kanematsu Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 552 Pages: 106-113

    • DOI

      10.1016/j.bbrc.2021.03.045

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of KS-133 as a novel bicyclic peptide with a potent and selective VIPR2 antagonist activity that counteracts cognitive decline in a mouse model of psychiatric disorders2021

    • Author(s)
      Sakamoto K, Chen L, Miyaoka T, Yamada M, Masutani T, Ishimoto K, Hino N, Nakagawa S, Asano S, Ago Y
    • Journal Title

      Frontiers in Pharmacology

      Volume: 12 Pages: 751587-751587

    • DOI

      10.3389/fphar.2021.751587

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Probing the VIPR2 microduplication linkage to schizophrenia in animal and cellular models2021

    • Author(s)
      Ago Y, Asano S, Hashimoto H, Waschek JA
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 717490-717490

    • DOI

      10.3389/fnins.2021.717490

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activation of the VPAC2 Receptor Impairs Axon Outgrowth and Decreases Dendritic Arborization in Mouse Cortical Neurons by a PKA-Dependent Mechanism2020

    • Author(s)
      Takeuchi Shuto、Kawanai Takuya、Yamauchi Ryosuke、Chen Lu、Miyaoka Tatsunori、Yamada Mei、Asano Satoshi、Hayata-Takano Atsuko、Nakazawa Takanobu、Yano Koji、Horiguchi Naotaka、Nakagawa Shinsaku、Takuma Kazuhiro、Waschek James A.、Hashimoto Hitoshi、Ago Yukio
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 521-532

    • DOI

      10.3389/fnins.2020.00521

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] The VIP/VIPR2 pathway regulates breast cancer cell migration2022

    • Author(s)
      Satoshi Asano, Misa Yamasaka, Kairi Ozasa, Kotaro Sakamoto, Atsuko Hayata-Takano, Takanobu Nakazawa, Hitoshi Hashimoto, James A. Waschek, Yukio Ago
    • Organizer
      VPAC ISBAP 2022 (Joint symposium of the 1st Meeting of the International Society for Bioactive Peptides and the 15th International Symposium on VIP, PACAP and Related Peptides)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neuron-specific overexpression of human VPAC2 receptors in mice causes cognitive dysfunction2022

    • Author(s)
      Ami Ono, Daichi Koan, Satoshi Asano, Tatsunori Miyaoka, Lu Chen, Mei Yamada, Shinsaku Nakagawa, Atsuko Hayata-Takano, Takanobu Nakazawa, Akihiro Harada, Hitoshi Hashimoto, James A. Waschek, Yukio Ago
    • Organizer
      VPAC ISBAP 2022 (Joint symposium of the 1st Meeting of the International Society for Bioactive Peptides and the 15th International Symposium on VIP, PACAP and Related Peptides)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経ペプチド受容体VIPR2のオリゴマー化とその機能的意義2022

    • Author(s)
      浅野智志, 小笹かいり, 中澤敬信, Waschek James, 吾郷由希夫
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 神経ペプチドVIPはVPAC2受容体を介するPI3K経路の活性化により細胞遊走を引き起こす2022

    • Author(s)
      小笹かいり, 浅野智志, 山坂美紗, 早田敦子, 中澤敬信, 橋本 均, Waschek James, 吾郷由希夫
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 神経発達障害モデルマウスにおける機械的アロディニアの発症とミクログリアの関与2022

    • Author(s)
      今戸瑛二, Samnang Sun, Abawa Abrar, 浅野智志, 中村庸輝, 中島一恵, 森岡徳光, 津賀一弘, 入舩正浩, 田熊一敞, 木口倫一, 吾郷由希夫
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] イミダゾールジペプチドの中枢作用に関する検討2022

    • Author(s)
      山口稜太, 山口拓海, 中川晋作, 浅野智志, 松浦圭介, 中川正則, 吾郷由希夫
    • Organizer
      日本薬学会第142年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] A potential role of neuropeptide receptor VIPR2 signaling in tumor cell migration2022

    • Author(s)
      Satoshi Asano, Misa Yamasaka, Kairi Ozasa, James Waschek, Yukio Ago
    • Organizer
      第55回広島大学歯学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Abnormal pain sensitivity associated with spinal microglial activation in a prenatal valproic acid-induced mouse model of autism2022

    • Author(s)
      Eiji Imado, Sun Samnang, Abrar Rizal Abawa, Satoshi Asano, Kazuhiro Tsuga, Masahiro Irifune, Yukio Ago
    • Organizer
      第55回広島大学歯学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] マウス胎生期のバルプロ酸曝露は脊髄でのミクログリアの増殖とアロディニアを引き起こす2022

    • Author(s)
      吾郷由希夫, 今戸瑛二, Samnang Sun, 中村庸輝, 中島一恵, 森岡徳光, 田熊一敞, 木口倫一, 浅野智志
    • Organizer
      Neuro2022 (第45回日本神経科学大会・第65回日本神経化学会大会・第32回日本神経回路学会大会 合同大会)
    • Related Report
      2022 Annual Research Report
  • [Presentation] Possible role of histone deacetylase inhibition in tactile hypersensitivity in a mouse model of autism spectrum disorder2022

    • Author(s)
      Samnang Sun, Eiji Imado, Tran Ngoc Bao Huynh, Yoki Nakamura, Kazue Hisaoka-Nakashima, Norimitsu Morioka, Norikazu Kiguchi, Satoshi Asano, Yukio Ago
    • Organizer
      第37回創薬・薬理フォーラム岡山
    • Related Report
      2022 Annual Research Report
  • [Presentation] 神経ペプチド受容体VIPR2はPI3K経路を介してがん細胞遊走を制御する2022

    • Author(s)
      浅野智志, 吾郷由希夫
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 鎮痛作用を示さない低用量μオピオイド受容体アゴニストは自閉スペクトラム症モデルマウスの社会性行動障害を改善する2022

    • Author(s)
      吾郷由希夫, 内藤 恵, 川瀬啓生, 樋口桃子, 山川英訓, 大波壮一郎, 小川公一, 中邨篤史, 河内貴弘, 今戸瑛二, 田原 孟, 浅野智志, 古武弥一郎, 田熊一敞, 橋本 均
    • Organizer
      第44回日本生物学的精神医学会年会、第32回日本臨床精神神経薬理学会年会、第52回日本神経精神薬理学会年会、第6回日本精神薬学会総会・学術集会 4学会合同年会(BPCNPNPPP4学会合同年会)
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胎生期のヒストン脱アセチル化酵素阻害は脊髄ミクログリアの活性化と機械的アロディニアを引き起こす2022

    • Author(s)
      今戸瑛二, Sun Samnang, Huynh Ngoc Bao Tran, 中村庸輝, 中島一恵, 森岡徳光, 木口倫一, 浅野智志, 吾郷由希夫
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] TRPV1アンタゴニストAMG517は胎生期バルプロ酸投与誘発の自閉症モデルマウスにおいて痛覚感受性の異常と社会性行動障害を改善する2022

    • Author(s)
      田原 孟, 今戸瑛二, 川瀬啓生, 樋口桃子, 山川英訓, 小川公一, 古武弥一郎, 田熊一敞, 橋本 均, 浅野智志, 吾郷 由希夫
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] PLC様タンパク質PRIP1のPH domain内包リポソームはシスプラチン耐性乳ガン細胞のアポトーシス細胞死を促進する2022

    • Author(s)
      浅野智志, 吾郷由希夫, 兼松 隆
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Regulation of tumor cell migration by vasoactive intestinal peptide (VIP)-VPAC2 receptor signaling2021

    • Author(s)
      Satoshi Asano, Misa Yamasaka, Kairi Ozasa, James A. Waschek, Yukio Ago
    • Organizer
      The 6th Joint Scientific Meeting in Dentistry
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Abnormal pain sensitivity in a prenatal valproic acid-induced mouse model of autism spectrum disorder2021

    • Author(s)
      Eiji Imado, Sun Samnang, Abrar Rizal Abawa, Satoshi Asano, Kazuhiro Tsuga, Masahiro Irifune, Yukio Ago
    • Organizer
      The 6th Joint Scientific Meeting in Dentistry
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Overexpression of VIPR2 in neurons causes defects in dendritic growth and cognitive impairment2021

    • Author(s)
      Tatsunori Miyaoka, Lu Chen, Mei Yamada, Daichi Koan, Satoshi Asano, Kenji Ishimoto, Shinsaku Nakagawa, Atsuko Hayata, Takanobu Nakazawa, Akihiro Harada, Hitoshi Hashimoto, James A. Waschek, Yukio Ago
    • Organizer
      The 7th Congress of the Asian College of Neuropsychopharmacology (AsCNP)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] A potent and highly selective VPAC2 receptor antagonist peptide KS-133 counteracts cognitive impairment in a mouse model relevant to schizophrenia2021

    • Author(s)
      Yukio Ago, Lu Chen, Tatsunori Miyaoka, Mei Yamada, Teruaki Masutani, Kenji Ishimoto, Shinsaku Nakagawa, Satoshi Asano, Kotaro Sakamoto
    • Organizer
      The 60th Annual Meeting of the American College of Neuropsychopharmacology (ACNP)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脳神経細胞 での VPAC2 受容体の過剰発現は認知機能障害を引き起こす2021

    • Author(s)
      古庵大地,今戸瑛二,浅野智志,ChenLu,宮岡辰典,山田めゐ,石本憲司,中川晋作, 早田敦子, 中澤敬信, 原田彰宏, 橋本 均, Waschek James, 吾郷由希夫
    • Organizer
      日本薬学会第 141 年会
    • Related Report
      2021 Research-status Report
  • [Presentation] VPAC2 受容体の制御する細胞遊走メカニズム2021

    • Author(s)
      山坂美紗, 浅野智志, 早田敦子, 中澤敬信, 橋本 均, Waschek James, 吾郷由希夫
    • Organizer
      日本薬学会第 141 年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 胎生期バルプロ酸投与マウスは熱刺激およびカプサイシン誘発痛の 増大と機械的アロディニアを示す2021

    • Author(s)
      今戸瑛二,浅野智志,中村庸輝,中島一恵,森岡徳光,津賀一弘,入舩正浩,田熊一 敞, 吾郷由希夫
    • Organizer
      第139回日本薬理学会近畿部会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒト VPAC2 受容体の過 剰発現を細胞種特異的かつ時空間的に制御可能な新しいトランスジェニックマウスモ デルの開発2021

    • Author(s)
      宮岡辰典, 陳 露, 山田めゐ, 古庵大地, 浅野智志, 石本憲司, 中川晋作, 早田敦子, 中澤敬信, 原田彰宏, 橋本 均, Waschek James, 吾郷由希夫
    • Organizer
      第 43 回日本生物学的精神医学会・第 51 回日本神経精神薬理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 神経ペプチドVIP-VPAC2受容体シグナルは、がん細胞遊走を 制御する新規の分子機構である2021

    • Author(s)
      浅野智志, 吾郷由希夫
    • Organizer
      第 63 回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 新規選択的 VPAC2 受容体アンタゴニストペプチドの創製と その中枢薬理作用2021

    • Author(s)
      山田めゐ, 陳 露, 宮岡辰典, 桝谷晃明, 石本憲司, 樋野展正, 中川晋作, 浅野智志, 坂元孝太郎, 吾郷由希夫
    • Organizer
      第 140 回日本薬理学会近畿部会
    • Related Report
      2021 Research-status Report
  • [Presentation] VPAC2受容体の制御する細胞遊走メカニズム2021

    • Author(s)
      山坂 美紗、浅野 智志、早田 敦子、中澤 敬信、橋本 均、Waschek James、吾郷 由希夫
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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