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Regulation of extracellular matrix remodeling induced by stellate cells and immune cells in the pancreatic tumor microenvironment

Research Project

Project/Area Number 26462062
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

NABAE Toshinaga  九州大学, 医学研究院, 共同研究員 (10467889)

Co-Investigator(Kenkyū-buntansha) 前山 良  九州大学, 医学研究院, 共同研究員 (10611668)
宮坂 義浩  九州大学, 大学病院, 助教 (40507795)
真鍋 達也  九州大学, 大学病院, 講師 (60546464)
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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords細胞外マトリックス / リモデリング / 膵星細胞 / 免疫細胞 / 低酸素環境 / PLOD2 / 脂肪由来幹細胞 / コラーゲンマトリックス / 好中球 / 脂肪組織由来幹細胞 / 膵癌
Outline of Final Research Achievements

The aim of this study was to clarify the mechanism and contribution of stellate cells and immune cells in of remodeling extracellular matrix of pancreatic cancer. We isolated activated stellate cells (PSCs) from human pancreatic cancer and analyzed the structure of collagen matrix produced by PSCs. Under hypoxic condition, the alignment of collagen fiber became parallel and enhanced motility of pancreatic cancer. We identified PLOD2 as a major collagen modifying enzyme under hypoxia. We also identified collagen matrix produced by PSCs was denser and stiffer than that of adipose tissue derived stromal cells, which means heterogeneity of stromal cells in pancreatic cancer influences mechanical structure of extracellular matrix in pancreatic cancer.

Report

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

Research Products

(10 results)

All 2016 2015 2014

All Journal Article Presentation

  • [Journal Article] Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility.2016

    • Author(s)
      Sada M, Ohuchida K, Horioka K, Okumura T, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Nakamura M
    • Journal Title

      Cancer letter

      Volume: 372 Pages: 1499-1508

    • DOI

      10.1016/j.canlet.2016.01.016

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL2016

    • Author(s)
      Chijiiwa Y, Moriyama T, Ohuchida K, Nabae T, Ohtsuka T, Miyasaka Y, Fujita H, Maeyama R, Manabe T, Abe A, Mizuuchi Y, Oda Y, Mizumoto K, Nakamura M
    • Journal Title

      Int J Oncol.

      Volume: 48 Pages: 1499-1508

    • DOI

      10.3892/ijo.2016.3389

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 低酸素下膵星細胞による癌間質マトリックス・リモデリングは膵癌浸潤能を増強する2016

    • Author(s)
      佐田政史、大内田研宙、阿部俊也、遠藤翔、肥川和寛、奥村隆志、千々岩芳朗、吉田真樹、堀岡宏平、森山大樹、宮坂義浩、大塚隆生、植木隆, 永井英司、水元一博、 小田義直、中村雅史
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      リーガロイヤルホテル大阪(大阪市)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 膵周囲脂肪組織は肝癌細胞の遊走・浸潤機能を増強し、局所浸潤に関与する2016

    • Author(s)
      奥村隆志、大内田研宙、武居晋、中山宏道、阿部俊也、遠藤翔、肥川和寛、千々岩芳朗、吉田真樹、鄭彪、佐田政史、堀岡宏平、森山大樹、三好圭、宮坂義浩、真鍋達也、大塚隆生、植木隆、永井英司、水元一博、中村雅史
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      リーガロイヤルホテル大阪(大阪市)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 膵星細胞は基質リモデリングにより、leading cellとして膵癌浸潤を先導する2016

    • Author(s)
      肥川和寛、大内田研宙、佐田政史、武居晋、中山宏道、阿部俊也、遠藤翔、奥村隆志、吉田真樹、千々岩芳朗、堀岡宏平、森山大樹、宮坂義浩、真鍋達也、大塚隆生、大内田理一、植木隆、永井英司、水元一博、中村雅史
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      リーガロイヤルホテル大阪(大阪市)
    • Year and Date
      2016-04-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Pancreatic Stellate Cells Lead and Promote the Local Invasion of Cancer Cells, by Physically Remodeling the Extracellular Matrix with Collagen Fiber Alignment in Pancreatic Cancer2015

    • Author(s)
      Koikawa K, Ohuchida K, Sada M, Abe T, Endo S, Horioka K, Moriyama T, Miyasaka Y, Ohtsuka T, Ohuchida R, Ueki T, Nagai E, Mizumoto K, Nakamura M
    • Organizer
      American Pancreatic Association 46th Annual Meeting
    • Place of Presentation
      San Diego(USA)
    • Year and Date
      2015-11-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵癌細胞の浸潤機序-浸潤を先導するleading cellsの同定・解析-2015

    • Author(s)
      肥川和寛、佐田政史、大内田研宙、阿部俊也、遠藤翔、真鍋達也、大塚隆生、高畑俊一、植木隆、永井英司、水元一博、中村雅史、田中雅夫
    • Organizer
      JDDW2015 第23回消化器関連学会週間
    • Place of Presentation
      東京都
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 脂肪組織由来幹細胞は膵癌細胞の遊走・浸潤を促進し悪性度に関与する2015

    • Author(s)
      奥村隆志、大内田研宙、阿部俊也、遠藤翔、肥川和寛、千々岩芳朗、吉田真樹、佐田政史、堀岡宏平、真鍋達也、大塚隆生、高畑俊一、植木隆、永井英司、水元一博、中村雅史、田中雅夫
    • Organizer
      JDDW2015 第23回消化器関連学会週間
    • Place of Presentation
      東京都
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 低酸素環境下膵星細胞はPLOD2誘導性間質リモデリングによって膵癌の浸潤を促進する2015

    • Author(s)
      佐田政史、大内田研宙、奥村隆志、千々岩芳朗、吉田真樹、田中友晴、堀岡宏平、鄭彪、水内祐介、藤原謙次、森山大樹、宮坂義浩、大塚隆生、高畑俊一、小田義直、水元一博、田中雅夫
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report
  • [Presentation] 膵癌間質の線維配列が癌細胞の形態と浸潤方向に与える影響2014

    • Author(s)
      佐田政史、大内田研宙、堀岡宏平、田中友晴、鄭彪、Cases AI、赤川進、藤原謙次、仲田興平、宮坂義浩、前山良、大塚隆生、高畑俊一、水元一博、田中雅夫
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2014-04-04
    • Related Report
      2014 Research-status Report

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

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