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Stellate cell-mediated regulation of stemness maintenance in pancreatic cancer stem cells

Research Project

Project/Area Number 23591008
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionTohoku University

Principal Investigator

MASAMUNE Atsushi  東北大学, 医学(系)研究科(研究院), 准教授 (90312579)

Co-Investigator(Kenkyū-buntansha) HAMADA Shin  東北大学, 大学院医学系研究科, 助教 (20451560)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords膵癌 / 膵炎 / マイクロRNA / 膵線維化 / シグナル伝達 / 薬剤耐性 / 膵星細胞 / 上皮間葉転換 / 遺伝子 / アンギオテンシン受容体拮抗剤 / 幹細胞 / stemness / 膵臓癌 / 癌幹細胞
Research Abstract

Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche. miR-210 was identified as an upregulated micro RNA by co-culture with PSCs. Inhibition of miR-210 expression decreased stem cell-like phenotypes in pancreatic cancer cells. Olmesartan, an angiotensin II type I receptor blocker, administrated at 10 mg/kg in drinking water inhibited the growth of subcutaneous tumors derived from the co-injection of pancreatic cancer cells and stellate cells. Olmesartan inhibited the growth of tumors by targeting stellate cell activities, and olmesartan might be useful as an anti-fibrosis therapy in pancreatic cancer.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (36 results)

All 2014 2013 2012 2011

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (15 results) (of which Invited: 1 results)

  • [Journal Article] Alteration of the microRNA expression profile during the activation of pancreatic stellate cells2014

    • Author(s)
      Masamune A, Nakano E, Hamada S, Takikawa T, Yoshida N, Shimosegawa T.
    • Journal Title

      Scand J Gastroenterol

      Volume: 49 Issue: 3 Pages: 323-331

    • DOI

      10.3109/00365521.2013.876447

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CUB-domain containing protein 1 represses the epithelial phenotype of pancreatic cancer cells2014

    • Author(s)
      Miura S, Hamada S, Masamune A, Satoh K, Shimosegawa T
    • Journal Title

      Exp Cell Res

      Volume: 321(2) Issue: 2 Pages: 209-218

    • DOI

      10.1016/j.yexcr.2013.12.019

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The zinc transporter LIV-1 is a novel regulator of stemness in pancreatic cancer cells2014

    • Author(s)
      Unno J, Masamune A, Hamada S, Shimosegawa T.
    • Journal Title

      Scand J Gastroenterol

      Volume: 49 Issue: 2 Pages: 215-221

    • DOI

      10.3109/00365521.2013.865075

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX2014

    • Author(s)
      Hamada S, Masamune A, Miura S, Satoh K, Shimosegawa T
    • Journal Title

      Cell Signal

      Volume: 26(2) Issue: 2 Pages: 179-185

    • DOI

      10.1016/j.cellsig.2013.11.003

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inflammation and pancreatic cancer: disease promoter and new therapeutic target.2014

    • Author(s)
      Hamada S, Masamune A, Shimosegawa T.
    • Journal Title

      J Gastroenterol.

      Volume: 49 Issue: 4 Pages: 605-617

    • DOI

      10.1007/s00535-013-0915-x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Variants in CPA1 are strongly associated with early onset chronic pancreatitis2013

    • Author(s)
      Witt H, Beer S, Rosendahl J, Chen JM, Chandak GR, Masamune A, Bence M, Szmola R, Oracz G, Macek M Jr, Bhatia E, Steigenberger S, Lasher D, Bühler F, Delaporte C, Tebbing J, Ludwig M, Pilsak C, Saum K, Bugert P, Masson E, Paliwal S, Bhaskar S, Sobczynska-Tomaszewska A, Bak D, Balascak I, Choudhuri G, Nageshwar Reddy D, Rao GV, Thomas V, Kume K, Nakano E, Kakuta Y, Shimosegawa T, Durko L, Szabó A, Schnúr A, Hegyi P, Rakonczay Z Jr, Pfützer R, Schneider A, Groneberg DA, Braun M, Schmidt H, Witt U, Friess H, Algül H, Landt O, Schuelke M, Krüger R, Wiedenmann B, Schmidt F, Zimmer KP, Kovacs P, Stumvoll M, Blüher M, Müller T, Janecke A, Teich N, Grützmann R, Schulz HU, Mössner J, Keim V, Löhr M, Férec C, Sahin-Tóth M.
    • Journal Title

      Nature Genet

      Volume: 45 Issue: 10 Pages: 1216-1220

    • DOI

      10.1038/ng.2730

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] miR-210 regulates the interaction between pancreatic cancer cells and stellate cells2013

    • Author(s)
      Takikawa T, Masamune A, Hamada S, Nakano E, Yoshida N, Shimosegawa T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 437 Issue: 3 Pages: 433-439

    • DOI

      10.1016/j.bbrc.2013.06.097

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pancreatic stellate cells - Multi-functional cells in the pancreas2013

    • Author(s)
      Masamune A, Shimosegawa T
    • Journal Title

      Pancreatology

      Volume: 13 Issue: 2 Pages: 102-105

    • DOI

      10.1016/j.pan.2012.12.058

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pancreatic stellate cells reduce insulin expression and induce apoptosis in pancreaticβ-cells2013

    • Author(s)
      Kikuta K, Masamune A, Hamada S, Takikawa T, Nakano E, Shimosegawa T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 433 Issue: 3 Pages: 292-7

    • DOI

      10.1016/j.bbrc.2013.02.095

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The angiotensin II type I receptor blocker olmesartan inhibits the growth of pancreatic cancer by targeting stellate cell activities in mice2013

    • Author(s)
      Masamune A, Hamada S, Kikuta K, Takikawa T, Miura S, Nakano E, Shimosegawa T.
    • Journal Title

      Scand J Gastroenterol

      Volume: 48 Issue: 5 Pages: 602-609

    • DOI

      10.3109/00365521.2013.777776

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] miR-197 induces epithelialmesenchymal transition in pancreatic cancer cells by targeting p120 catenin. J Cell Physiol2013

    • Author(s)
      Hamada S, et al
    • Journal Title

      J Cell Physiol

      Volume: 228(6) Issue: 6 Pages: 1255-63

    • DOI

      10.1002/jcp.24280

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transforming growth factor-α activates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation2013

    • Author(s)
      Tahara H, Sato K, Yamazaki Y, Ohyama T, Horiguchi N, Hashizume H, Kakizaki S, Takagi H, Ozaki I, Arai H, Hirato J, Jesenofsky R, Masamune A, Mori M
    • Journal Title

      Lab Invest

      Volume: 93 Issue: 6 Pages: 720-732

    • DOI

      10.1038/labinvest.2013.59

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Connexins regulate cell functions in pancreatic stellate cells2013

    • Author(s)
      Masamune A, Suzuki N, Kikuta K, Ariga H, Hayashi S, Takikawa T, Kume K, Hamada S, Hirota M, Kanno A, Egawa S, Unno M, Shimosegawa T.
    • Journal Title

      Pancreas

      Volume: 42 Issue: 2 Pages: 308-316

    • DOI

      10.1097/mpa.0b013e31825c51d6

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel therapeutic strategies targeting tumor-stromal interactions in pancreatic cancer2013

    • Author(s)
      Hamada S, Masamune A, Shimosegawa T
    • Journal Title

      Front Physiol

      Volume: 4 Pages: 331-331

    • DOI

      10.3389/fphys.2013.00331

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alteration of pancreatic cancer cell functions by tumor-stromal cell interaction2013

    • Author(s)
      Hamada S, Masamune A, Shimosegawa T
    • Journal Title

      Front Physiol

      Volume: 4 Pages: 318-318

    • DOI

      10.3389/fphys.2013.00318

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of novel missense CTRC variants in Japanese patients with chronic pancreatitis2013

    • Author(s)
      Masamune A, Nakano E, Kume K, Kakuta Y, Ariga H, Shimosegawa T
    • Journal Title

      Gut

      Volume: 62 Issue: 4 Pages: 653-654

    • DOI

      10.1136/gutjnl-2012-303860

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pancreatic stellate cells reduce insulin expression and induce apoptosis in pancreatic β-cells2013

    • Author(s)
      Kikuta K, Masamune A, Hamada S, Takikawa T, Nakano E, Shimosegawa T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells2012

    • Author(s)
      Hamada S, Masamune A, Takikawa T, Suzuki N, Kikuta K, Hirota M, Hamada H, Kobune M, Satoh K, Shimosegawa T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 421(2) Issue: 2 Pages: 349-354

    • DOI

      10.1016/j.bbrc.2012.04.014

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] StellaTUM : current consensus and discussion on pancreatic stellate cell research2012

    • Author(s)
      Erkan M, Adler G, Apte MV, Bachem MG, Buchholz M, Detlefsen S, Esposito I, Friess H, Gress TM, Habisch HJ, Hwang RF, Jaster R, Kleeff J, Klöppel G, Kordes C, Logsdon CD, Masamune A, Michalski CW, Oh J, Phillips PA, Pinzani M, Reiser-Erkan C, Tsukamoto H, Wilson J.
    • Journal Title

      Gut.

      Volume: 61 Issue: 2 Pages: 172-178

    • DOI

      10.1136/gutjnl-2011-301220

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulators of epithelial mesenchymal transition in pancreatic cancer2012

    • Author(s)
      Hamada S, Satoh K, Masamune A, Shimosegawa T
    • Journal Title

      Front Physiol

      Volume: 3 Pages: 254-254

    • DOI

      10.3389/fphys.2012.00254

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] StellaTUM: current consensus and discussion on pancreatic stellate cell research.2012

    • Author(s)
      Erkan M, Adler G, Apte MV, et al.
    • Journal Title

      Gut

      Volume: 61 Pages: 172-178

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] ビタミンDは膵星細胞をターゲットとして膵線維化を抑制する2013

    • Author(s)
      正宗淳,下瀬川徹
    • Organizer
      第21回日本消化器関連学会週間
    • Place of Presentation
      東京
    • Year and Date
      2013-10-11
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Pancreatic stellate cells -multi-function cells in the pancreas-2013

    • Author(s)
      Masamune A.
    • Organizer
      17th International Symposium on the Cells of the Hepatic Sinusoid
    • Place of Presentation
      大阪
    • Year and Date
      2013-09-24
    • Related Report
      2013 Final Research Report
  • [Presentation] Pancreatic stellate cells induceβ-cell dysfunction and apoptosis–a novel mechanism of diabetes in diseased pancreas-2013

    • Author(s)
      Masamune A, Kikuta K, Hamada S, Nakano E, Shimosegawa T.
    • Organizer
      Digestive Disease Week 2013, the American Gastroenterological Association
    • Place of Presentation
      アメリカ合衆国オーランド
    • Year and Date
      2013-05-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of microRNAs in the interactions between pancreatic stellate cells2013

    • Author(s)
      Takikawa T, Masamune A, Hamada S, Nakano E, Shimosegawa T
    • Organizer
      Digestive Disease Week 2013, the American Gastroenterological Association
    • Place of Presentation
      Orlando, FL, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pancreatic stellate cells induce β-cell dysfunction and apoptosis; a novel mechanism of diabetes in diseased pancreas-2013

    • Author(s)
      Masamune A, Kikuta K, Hamada S, Nakano E, Shimosegawa T
    • Organizer
      Digestive Disease Week 2013, the American Gastroenterological Association
    • Place of Presentation
      Orlando, FL, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pancreatic stellate cell contributes to the maintenance of cancer stem cell-like phenotype in pancreatic cancer cells2013

    • Author(s)
      Hamada S, Masamune A, Satoh K, Shimosegawa T
    • Organizer
      国際膵臓フォーラム2013
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] “Fibrosis in Extrahepatic Organ” : Pancreas2013

    • Author(s)
      Masamune A
    • Organizer
      17th International Symposium on the Cells of the Hepatic Sinusoid
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pancreatic stellate cells -Multi-functional cells in the pancreas-. American Pancreatic Association/International Pancreatic Association2012

    • Author(s)
      Masamune A.
    • Organizer
      2012 Joint Meeting
    • Place of Presentation
      アメリカ合衆国マイアミ
    • Year and Date
      2012-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵星細胞は膵癌細胞の癌幹細胞様形質を増強する2012

    • Author(s)
      滝川哲也,正宗淳,濱田晋,海野純,鈴木範明,粂潔,菊田和宏,菅野敦,廣田衛久,佐藤賢一,下瀬川徹
    • Organizer
      第20回日本消化器関連学会週間
    • Place of Presentation
      神戸
    • Year and Date
      2012-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Pancreatic Stellate Cells Express Inducible Nitric Oxide Synthase2012

    • Author(s)
      Suzuki N, Masamune A, Kikuta K, Takikawa T, Hayashi S, Shimosegawa T.
    • Organizer
      2012 Annual Meeting of the American Gastroenterological Association
    • Place of Presentation
      アメリカ合衆国サンディエゴ
    • Year and Date
      2012-05-20
    • Related Report
      2013 Final Research Report
  • [Presentation] MicroRNA Profiles Are Altered During the Activation in Pancreatic Stellate Cells2012

    • Author(s)
      Masamune A, Suzuki S, Kikuta K, Takikawa T, Hayashi S, Ariga H, Shimosegawa T.
    • Organizer
      2012 Annual Meeting of the American Gastroenterological Association
    • Place of Presentation
      アメリカ合衆国サンディエゴ
    • Year and Date
      2012-05-20
    • Related Report
      2013 Final Research Report
  • [Presentation] MicroRNA profiles are altered during the activation in pancreatic stellate cells2012

    • Author(s)
      Masamune A, Suzuki N, Kikuta K, Takikawa T, Ariga H, Shimosegawa T
    • Organizer
      Digestive Diseases Week 2012
    • Place of Presentation
      San Diego, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Pancreatic stellate cells -Multifunctional cells in the pancreas-2012

    • Author(s)
      Masamune A, Shimosegawa T
    • Organizer
      2012 Annual meeting of the American Pancreatic Association/International Pancreatic Association
    • Place of Presentation
      Miami, USA
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 膵星細胞活性化に伴い広範なmicroRNA発現プロファイルの変化がおこる2012

    • Author(s)
      正宗 淳、下瀬川徹
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵星細胞はbeta1-integrinシグナル系を介して膵癌細胞の放射線感受性を減弱させる.2011

    • Author(s)
      正宗 淳、下瀬川徹
    • Organizer
      J-DDW
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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