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Elucidation of leading cell and cancer microenvironment normalization of pancreatic cancer

Research Project

Project/Area Number 26293305
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

OHUCHIDA Kenoki  九州大学, 大学病院, 助教 (20452708)

Co-Investigator(Kenkyū-buntansha) 大塚 隆生  九州大学, 大学病院, 講師 (20372766)
村田 正治  九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (30304744)
前山 良  九州大学, 医学(系)研究科(研究院), 共同研究員 (10611668)
田中 雅夫  九州大学, 医学(系)研究科(研究院), 教授 (30163570)
江上 拓哉  九州大学, 医学(系)研究科(研究院), 共同研究員 (40507787)
宮坂 義浩  九州大学, 医学(系)研究科(研究院), 助教 (40507795)
真鍋 達也  九州大学, 医学(系)研究科(研究院), 助教 (60546464)
坂井 寛  九州大学, 医学(系)研究科(研究院), 共同研究員 (80611665)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
KeywordsPancreatic cancer / PSCs / Leading cell / ECM remodeling / Cancer micro environment / Normalization / 膵癌 / 膵星細胞 / 細胞外マトリックス / leading cell / 基質リモデリング
Outline of Final Research Achievements

We established 3D in vitro collagen invasion assay to investigate leading cell. We found that Pancreatic stellate cells (PSCs) frequently invaded a collagen matrix with cancer cells, which invaded behind the invading PSCs, and an increase in the number of invading cancer cells in co-cultures with PSCs. Invading PSCs changed the alignment of collagen fibers, resulting in ECM remodeling and an increase in the parallel fibers along the direction of invading PSCs. We elucidate that one of the ECM remodeling factor of PSCs is Endo180. Endo180 knockdown in PSCs attenuated the invasive abilities of PSCs and co-cultured cancer cells, and decreased the expression level of phosphorylated myosin light chain 2 (MLC2). Our findings suggest that PSCs lead the local invasion of pancreatic cancer cells by physically remodeling the ECM, possibly via the function of Endo180, which reconstructs the actin cell skeleton by phosphorylation of MLC2.

Report

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

Research Products

(20 results)

All 2016 2015 2014

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 6 results) Presentation (10 results) (of which Int'l Joint Research: 3 results) Book (2 results)

  • [Journal Article] (The) Calpain inhibitor calpeptin suppresses pancreatic cancer by disrupting cancer-stromal interactions in a mouse xenograft model2016

    • Author(s)
      Yoshida M, Miyasaka Y, Ohuchida Kenoki, Okumura T, Zheng B, Torata N, Fujita H, Nabae T, Manabe T, Shimamoto M, Ohtsuka T, Mizumoto K, Nakamura M
    • Journal Title

      Cancer Sci.

      Volume: 107 Pages: 1443-1452

    • DOI

      10.1111/cas.13024

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility2016

    • 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 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer2016

    • Author(s)
      Horioka K, Ohuchida K, Sada M, Zheng B, Moriyama T, Fujita H, Manabe T, Ohtsuka T, Shimamoto M, Miyazaki T, Mizumoto K, Oda Y, Nakamura M.
    • Journal Title

      International Journal of Oncology

      Volume: 48 Pages: 1499-1508

    • DOI

      10.3892/ijo.2016.3374

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 膵癌の浸潤・転移における癌微小環境の新たな役割2015

    • Author(s)
      大内田研宙、大塚隆生、橋爪誠、中村雅史
    • Journal Title

      胆と膵

      Volume: 36 Pages: 1181-1187

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Pancreatic Cancer: Clinical Significance of Biomarkers2014

    • Author(s)
      Mori M, Chiba T, Nakamizo A, Kumashiro R, Murata M, Akahoshi T, Tomikawa M, Ohuchida K, Ohtsuka T,Mizumoto K, Hashizume M,Tanaka M
    • Journal Title

      GastroIntestinal Tumors

      Volume: 1 Pages: 33-40

    • DOI

      10.1159/000354996

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer.2014

    • Author(s)
      Akagawa S, Ohuchida K, Torata N, Hattori M, Eguchi D, Fujiwara K, Kozono S, Cui L, Ikenaga N, Ohtsuka T, Oishima S, Mizumoto K, Oda Y, Tanaka M
    • Journal Title

      International Journal of Oncology

      Volume: 45 Pages: 113-120

    • DOI

      10.3892/ijo.2014.2391

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Micro RNA-373 is Down-regulated in Pancreatic Cancer and Inhibits Cancer Cell Invasion2014

    • Author(s)
      Nakata K, Ohuchida K, Mizumoto K, Aishima S, Oda Y, Nagai E, Tanaka M
    • Journal Title

      Annals of Surgical Oncology

      Volume: 21

    • DOI

      10.1245/s10434-014-3676-8

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells.2014

    • Author(s)
      Fujiwara K, Ohuchida K, Sada M, Horioka K, Ulrich CD 3rd, Shindo K, Ohtsuka T, Takahata S, Mizumoto K, Oda Y, Tanaka M.
    • Journal Title

      CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells

      Volume: 9 Pages: 1-11

    • DOI

      10.1371/journal.pone.0107247

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Endo180 regulate phosphorylation of myosin light chain 2 activity and increase the ability of extracellular matrix remodeling in leading pancreatic stellate cells.2016

    • Author(s)
      Koikawa K, Ohuchida K, Kibe S, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Okumura T, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Nakamura M.
    • Organizer
      The 47th Annual meeting of American Pancreatic Association
    • Place of Presentation
      Boston(USA)
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵癌浸潤を先導するleading cell‐膵星細胞の基質リモデリング機能と浸潤機序の解明‐2016

    • Author(s)
      肥川和寛
    • Organizer
      第71回日本消化器外科学会総会
    • Place of Presentation
      アスティ徳島(徳島市)
    • Year and Date
      2016-07-15
    • Related Report
      2016 Annual Research Report
  • [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、阿部俊也、遠藤翔、奥村隆志、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 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Suppression of CD51 in Pancreatic Stellate Cells Inhibits Tumor Growth by Reducing Stroma and Altering Tumor-Stromal Interaction in Pancreatic Cancer2015

    • Author(s)
      Horioka K, Ohuchida K, Sada M, Zheng B, Ohtsuka T, Ueki T, Nagai E, Mizumoto K, Oda Y, Nakamura M
    • Organizer
      American Pancreatic Association 46th Annual Meeting
    • Place of Presentation
      San Diego(USA)
    • Year and Date
      2015-11-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [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 Annual Research Report
  • [Presentation] 膵癌細胞は腹膜中皮細胞と相互作用により腹膜播種を促進する2015

    • Author(s)
      阿部俊也、大内田研宙、遠藤翔、肥川和寛、吉田真樹、千々岩芳朗、奥村隆志、田中友晴、佐田政史、堀岡宏平、藤原謙次、森山大樹、宮坂義浩、大塚隆生、高畑俊一、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 Annual Research Report
  • [Presentation] 膵癌細胞からの作用により膵星細胞中のNPAS1が増加する2014

    • Author(s)
      藤原謙次、大内田研宙、赤川進、大塚隆夫、高畑俊一、水元一博、田中雅夫
    • Organizer
      第45回日本膵臓学会大会
    • Place of Presentation
      北九州市
    • Year and Date
      2014-07-11
    • Related Report
      2014 Annual Research 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 Annual Research Report
  • [Book] 【膵炎・膵がん】膵がん浸潤・転移における微小環境の病態2016

    • Author(s)
      大内田研宙、中村雅史
    • Total Pages
      250
    • Publisher
      最新医学社
    • Related Report
      2016 Annual Research Report
  • [Book] Annual Review 2014 消化器2014

    • Author(s)
      佐田政史、水元一博、大内田研宙、大塚隆生、田中雅夫
    • Total Pages
      306
    • Publisher
      中外医学社
    • Related Report
      2014 Annual Research Report

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

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