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The effect of ionizing radiation on secretory phenotype of cancer-associated fibroblasts and its impact on cancer pathophysiology

Research Project

Project/Area Number 26461875
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionHokkaido University

Principal Investigator

Yamamori Tohru  北海道大学, 獣医学研究科, 准教授 (00512675)

Co-Investigator(Kenkyū-buntansha) 安井 博宣  北海道大学, アイソトープ総合センター, 准教授 (10570228)
高木 哲  北海道大学, 獣医学研究科, 准教授 (50396305)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords癌関連線維芽細胞 / 放射線 / サイトカイン / 活性酸素種 / 癌 / 細胞老化 / 老化関連分泌形質 / NADPHオキシダーゼ / 腫瘍間質
Outline of Final Research Achievements

Recent evidence suggests that cancer-associated fibroblasts (CAFs), which are the most abundant cell type in cancer stroma, and CAF-derived secretory factors play important roles in various aspects of cancer pathophysiology. This study was aimed to understand how ionizing radiation influences on CAFs and their secretory phenotype. We revealed that X-irradiation to mouse embryonic fibroblasts (MEFs) increased the number of senescent cells, which are reported to have similar characteristics to CAFs. This event was accompanied by the induction of multiple cytokines. We also found that X-irradiation enhanced cellular oxidative stress level and NADPH oxidase 4 protein (NOX4) was in part responsible for it. Furthermore, our data suggested that NOX4 was not involved in the induction of secretory factors in irradiated MEFs.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (42 results)

All 2017 2016 2015 2014 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 7 results) Presentation (28 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Remarks (3 results)

  • [Journal Article] Lipophilic tetraphenylphosphonium derivatives enhance radiation-induced cell killing via inhibition of mitochondrial energy metabolism in tumor cells2017

    • Author(s)
      Yasui H, Yamamoto K, Suzuki M, Sakai Y, Bo T, Nagane M, Nishimura E, Yamamori T, Yamasaki T, Yamada K, Inanami O
    • Journal Title

      Cancer Letters

      Volume: 390 Pages: 160-167

    • DOI

      10.1016/j.canlet.2017.01.006

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts.2016

    • Author(s)
      Yamamori T, Sasagawa T, Ichii O, Hiyoshi M, Bo T, Yasui H, Kon Y, Inanami O.
    • Journal Title

      Journal of Radiation Research

      Volume: - Issue: 3 Pages: 1-10

    • DOI

      10.1093/jrr/rrw113

    • NAID

      120006331861

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A nucleoside anticancer drug, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine, induces depth-dependent enhancement of tumor cell death in spread-out bragg peak (SOBP) of proton beam.2016

    • Author(s)
      Maeda K, Yasui H, Yamamori T, Matsuura T, Takao S, Suzuki M, Matsuda A, Inanami O, Shirato H.
    • Journal Title

      PLoS One

      Volume: 11(11) Issue: 11 Pages: e0166848-e0166848

    • DOI

      10.1371/journal.pone.0166848

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effect of MPS1 inhibition on genotoxic stress responses in murine tumour cells.2016

    • Author(s)
      Suzuki M, Yamamori T, Yasui H, Inanami O.
    • Journal Title

      Anticancer Research

      Volume: 36(6) Pages: 2783-2792

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro.2016

    • Author(s)
      Maeda K, Yasui H, Matsuura T, Suzuki M, Nam JM, Yamamori T, Inanami O, Shirato H.
    • Journal Title

      Journal of Radiation Research

      Volume: - Issue: 3 Pages: 307-311

    • DOI

      10.1093/jrr/rrv101

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) impairs mitochondrial fission and mitotic catastrophe after x-irradiation.2015

    • Author(s)
      Yamamori T., Ike S., Bo T., Sasagawa T., Sakai Y., Suzuki M., Yamamoto K., Nagane M., Yasui H., Inanami O.
    • Journal Title

      Mol. Biol. Cell.

      Volume: 26 Issue: 25 Pages: 4607-17

    • DOI

      10.1091/mbc.e15-03-0181

    • NAID

      120005677771

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of ROS and PKC-betaII in ionizing radiation-induced eNOS activation in human vascular endothelial cells.2015

    • Author(s)
      Sakata K, Kondo T, Mizuno N, Shoji M, Yasui H, Yamamori T, Inanami O, Yokoo H, Yoshimura N, Hattori Y.
    • Journal Title

      Vascular Pharmacology

      Volume: - Pages: 55-65

    • DOI

      10.1016/j.vph.2015.03.016

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Downregulation of the DNA repair enzyme apurinic/apyrimidinic endonuclease 1 stimulates transforming growth factor-β1 production and promotes actin rearrangement.2015

    • Author(s)
      Sakai Y., Yamamori T., Yasui H., and Inanami O.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 印刷中 Issue: 1 Pages: 35-41

    • DOI

      10.1016/j.bbrc.2015.03.163

    • NAID

      120005757980

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway.2015

    • Author(s)
      Nagane M., Yasui H., Sakai Y., Yamamori T., Niwa K., Hattori Y., Kondo T., and Inanami O.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 456 Issue: 1 Pages: 541-546

    • DOI

      10.1016/j.bbrc.2014.12.002

    • NAID

      120005906762

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Radiosensitization of tumor cells through endoplasmic reticulum stress induced by PEGylated nanogel containing gold nanoparticles.2014

    • Author(s)
      Yasui H, Takeuchi R, Nagane M, Meike S, Nakamura Y, Yamamori T, Ikenaka Y, Kon Y, Murotani H, Oishi M, Nagasaki Y, Inanami O
    • Journal Title

      Cancer Letters

      Volume: 347 Issue: 1 Pages: 151-158

    • DOI

      10.1016/j.canlet.2014.02.005

    • NAID

      120005425361

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 3-Methyl pyruvate enhances radiosensitivity through increasing mitochondria-derived reactive oxygen species in tumor cell lines2014

    • Author(s)
      Nishida N, Yasui H, Nagane M, Yamamori T, InanamiO.
    • Journal Title

      J Radiat Res

      Volume: (in press) Issue: 3 Pages: 455-463

    • DOI

      10.1093/jrr/rrt142

    • NAID

      120005457025

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新規Chk1阻害剤MK-8776による放射線増感効果とその誘導機構の解析2017

    • Author(s)
      山盛徹、鈴木基史、房知輝、酒井友里、稲波修
    • Organizer
      第19回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良県文化会館・奈良県奈良市
    • Year and Date
      2017-02-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 放射線照射後のDrp1リン酸化を実行する責任キナーゼの解明2016

    • Author(s)
      房知輝、山盛徹、髭白侑香、酒井友里、鈴木基史、稲波修
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      JMSアステールプラザ・広島県広島市
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新規Chk1阻害剤MK-8776の放射線増感剤としての効果の検討2016

    • Author(s)
      鈴木基史、山盛徹、稲波修
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      JMSアステールプラザ・広島県広島市
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] X線照射はミトコンドリア生合成を亢進することなく細胞内ミトコンドリア含量を増大させる2016

    • Author(s)
      山盛徹、笹川朋哉、市居修、房知輝、昆泰寛、稲波修
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      JMSアステールプラザ・広島県広島市
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] X線照射したヒト子宮頸がん由来HeLa細胞におけるミトコンドリア機能を中心としたエネルギー代謝応答の解析2016

    • Author(s)
      山本久美子、池中良徳、一瀬貴大、石塚真由美、安井博宣、鵜飼光子、山盛徹、稲波修
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学湘南キャンパス・神奈川県藤沢市
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 放射線によるストレス誘発性早期老化に伴う活性酸素種産生におけるNOXファミリータンパク質の寄与の検討2016

    • Author(s)
      酒井友里、山盛徹、日吉美恵、鈴木基史、稲波修
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学湘南キャンパス・神奈川県藤沢市
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA修復酵素APエンドヌクレアーゼ1のミトコンドリアでの過剰発現による酸化ストレス抵抗性発現メカニズムの解析2016

    • Author(s)
      山盛徹、玉置光、稲波修
    • Organizer
      第69回日本酸化ストレス学会学術集会
    • Place of Presentation
      仙台国際センター・宮城県仙台市
    • Year and Date
      2016-08-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒト子宮頸部がんHeLa細胞における放射線照射後のエネルギー産生とその意義2016

    • Author(s)
      稲波修、山本久美子、西村英里、房知輝、酒井友里、鈴木基史、池中良徳、一瀬貴大、石塚真由美、安井博宣、鵜飼光子、山田健一、山崎俊栄、山盛徹
    • Organizer
      第54回日本放射線腫瘍学会生物部会学術大会
    • Place of Presentation
      I-site なんば・大阪府大阪市
    • Year and Date
      2016-07-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] X線照射したがん細胞のESRオキシメトリーを用いた酸素消費率を指標としたミトコンドリア機能の解析2015

    • Author(s)
      山本久美子、安井博宣、山盛徹、中村秀夫、鵜飼光子、稲波修
    • Organizer
      第54回電子スピンサイエンス学会年会
    • Place of Presentation
      朱鷺メッセ 新潟コンベンションセンター・新潟県新潟市
    • Year and Date
      2015-11-02
    • Related Report
      2015 Research-status Report
  • [Presentation] MPS1阻害によるスピンドル形成チェックポイントの抑制がX線の殺細胞効果に与える影響の解析2015

    • Author(s)
      鈴木基史、山盛徹、安井博宣、稲波修
    • Organizer
      日本放射線影響学会ワークショップ
    • Place of Presentation
      富山大学五福キャンパス・富山県富山市
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl) cytosine (ECyd)併用による陽子線増感治療の実現に向けた基礎研究2015

    • Author(s)
      前田憲一郎、安井博宣、山盛徹、松浦妙子、高尾聖心、鈴木基史、松田彰、稲波修、白𡈽博樹
    • Organizer
      日本放射線影響学会ワークショップ
    • Place of Presentation
      富山大学五福キャンパス・富山県富山市
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] ミトコンドリア指向性化合物における分子骨格と放射線増感作用との相関性に関する研究2015

    • Author(s)
      安井博宣、西村英里、山盛徹、山本久美子、鵜飼光子、山崎俊栄、山田健一、稲波修
    • Organizer
      日本放射線影響学会ワークショップ
    • Place of Presentation
      富山大学五福キャンパス・富山県富山市
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] MPS1 を介したスピンドル形成チェックポイントが哺乳動物細胞の化学療法剤 感受性に与える影響の解析2015

    • Author(s)
      鈴木基史、山盛徹、安井博宣、稲波修
    • Organizer
      第158回日本獣医学会学術集会
    • Place of Presentation
      北里大学獣医学部キャンパス・青森県十和田市
    • Year and Date
      2015-09-07
    • Related Report
      2015 Research-status Report
  • [Presentation] 放射線照射後のミトコンドリア分裂におけるDrp1リン酸化の意義2015

    • Author(s)
      房知輝、山盛徹、池悟志、鈴木基史、酒井友里、安井博宣、稲波修
    • Organizer
      第158回日本獣医学会学術集会
    • Place of Presentation
      北里大学獣医学部キャンパス・青森県十和田市
    • Year and Date
      2015-09-07
    • Related Report
      2015 Research-status Report
  • [Presentation] 転写調節因子Id1ノックダウンが放射線感受性に与える影響とそのメカニズムの解明2015

    • Author(s)
      竹内麻依、安井博宣、鈴木基史、酒井友里、山盛徹、稲波修
    • Organizer
      第158回日本獣医学会学術集会
    • Place of Presentation
      北里大学獣医学部キャンパス・青森県十和田市
    • Year and Date
      2015-09-07
    • Related Report
      2015 Research-status Report
  • [Presentation] Inhibition of the mitochondrial fission protein dynamin-related protein 1 impairs mitotic catastrophe after X-irradiation2015

    • Author(s)
      Tohru Yamamori, Satoshi Ike, Tomoki Bo, Tomoya Sasagawa, Motofumi Suzuki, Yuri Sakai, Hironobu Yasui, Osamu Inanami
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      国立京都国際会館・京都府京都市
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Drp1 phosphorylation at Ser616 but not Ser637 is required for radiation-induced mitochondrial fission.2015

    • Author(s)
      Tomoki Bo, Tohru Yamamori, Satoshi Ike, Motofumi Suzuki, Yuri Sakai, HironobuYasui, Osamu Inanami
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      国立京都国際会館・京都府京都市
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] MPS1 inhibitors enhance chemosensitivity to etoposide and paclitaxel but not radiosensitivity in murine SCCVII cells2015

    • Author(s)
      Motofumi Suzuki, Tohru Yamamori, Hironobu Yasui, Osamu Inanami
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      国立京都国際会館・京都府京都市
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effect of intermittent hypoxia on the cellular sensitivities to X-irradiation and to boron neutron capture reaction in rat glioma cells2015

    • Author(s)
      Hironobu Yasui, Masaki Nagane, Tohru Yamamori, Ryoichi Hirayama, Natsuko Kondo, Shin-ichiro Masunaga, Osamu Inanami
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      国立京都国際会館・京都府京都市
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The relationship between radiation-induced cell cycle arrest and reactive oxygen species production from mitochondria2015

    • Author(s)
      Tohru Yamamori, Hironobu Yasui, Osamu Inanami
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      国立京都国際会館・京都府京都市
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Radiosensitizing effect by mitochondria-targeted nitroxides in tumor cells2015

    • Author(s)
      Hironobu Yasui, Eri Nishimura, Masaki Nagane, Tomoya Sasagawa, Tohru Yamamori, Toshihide Yamasaki, Ken-ichi Yamada, Osamu Inanami
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      国立京都国際会館・京都府京都市
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] DNA修復酵素APエンドヌクレアーゼ1の発現抑制による細胞外マトリックス関連遺伝子発現および細胞機能への影響2014

    • Author(s)
      酒井 友里、山盛 徹、安井 博宣、稲波 修
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-16
    • Related Report
      2014 Research-status Report
  • [Presentation] Drp1依存性ミトコンドリア分裂が細胞の放射線応答に与える影響の評価とそのメカニズムの解析2014

    • Author(s)
      山盛徹、池悟志、笹川朋哉、鈴木基史、酒井友里、安井博宣、稲波修
    • Organizer
      日本放射線影響学会 第57回大会
    • Place of Presentation
      鹿児島県民交流センター(鹿児島県鹿児島市)
    • Year and Date
      2014-10-01
    • Related Report
      2014 Research-status Report
  • [Presentation] DNA修復酵素APエンドヌクレアーゼ1の発現抑制による細胞外マトリックス関連遺伝子発現への影響とそれに伴う細胞機能の変化2014

    • Author(s)
      酒井 友里、山盛 徹、安井 博宣、稲波 修
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学 高等教育推進機構(北海道札幌市)
    • Year and Date
      2014-09-10
    • Related Report
      2014 Research-status Report
  • [Presentation] ミトコンドリア指向性ニトロキシドが放射線感受性に及ぼす影響2014

    • Author(s)
      西村英里、安井博宣、永根大幹、笹川朋哉、山盛 徹、山田健一、稲波 修
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学 高等教育推進機構(北海道札幌市)
    • Year and Date
      2014-09-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Drp1を介したミトコンドリア形態変化が細胞の放射線感受性に与える影響の評価とそのメカニズムの解析2014

    • Author(s)
      池 悟志、山盛 徹、鈴木 基史、酒井 友里、安井 博宣、稲波 修
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学 高等教育推進機構(北海道札幌市)
    • Year and Date
      2014-09-10
    • Related Report
      2014 Research-status Report
  • [Presentation] MPS1を介したスピンドル形成チェックポイントが哺乳動物細胞の放射線/化学療法剤感受性に与える影響の解析2014

    • Author(s)
      鈴木基史、山盛徹、安井博宣、稲波修
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学 高等教育推進機構(北海道札幌市)
    • Year and Date
      2014-09-10
    • Related Report
      2014 Research-status Report
  • [Presentation] ミトコンドリア指向性ニトロキシドが放射線感受性に及ぼす影響2014

    • Author(s)
      西村英里、安井博宣、永根大幹、笹川朋哉、山盛 徹、山崎俊栄、山田健一、稲波 修
    • Organizer
      第67回日本酸化ストレス学会学術集会
    • Place of Presentation
      同志社大学 今出川キャンパス良心館(京都府京都市)
    • Year and Date
      2014-09-04
    • Related Report
      2014 Research-status Report
  • [Remarks] 北海道大学大学院獣医学研究院放射線学教室ホームページ

    • URL

      https://www.vetmed.hokudai.ac.jp/organization/radbiol/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 北海道大学大学院獣医学研究科環境獣医科学講座放射線学教室ホームページ

    • URL

      http://www.hucc.hokudai.ac.jp/~k21820/index.html

    • Related Report
      2015 Research-status Report
  • [Remarks] 北海道大学獣医学研究科環境獣医科学講座放射線学教室

    • URL

      http://vetradserver.vetmed.hokudai.ac.jp/radiobiol/index.html

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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