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Clarification and control of immune cell-induced PSC substrate remodeling using KPCL mice

Research Project

Project/Area Number 17K10700
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

ONIMARU Manabu  九州大学, 医学研究院, 共同研究員 (80529876)

Co-Investigator(Kenkyū-buntansha) 三好 圭  九州大学, 大学病院, 助教 (70755272)
寅田 信博  九州大学, 大学病院, 臨床検査技師 (00398075)
大内田 研宙  九州大学, 大学病院, 講師 (20452708)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords膵癌 / 膵星細胞 / リモデリング / 癌微小環境 / 膵微小環境 / 癌間質相互作用 / 免疫細胞
Outline of Final Research Achievements

Focusing on the fact that remodeling of extracellular matrix abundant in pancreatic cancer tissues is involved in cancer invasion and metastasis, we analyzed the substrate remodeling centering on PSC (pancreatic stellate cells).
For the PSC, we have clarified the relationship between Endo180 expression in PSC and extracellular matrix, between MMP2 secretion / MT1MMP expression and basement membrane infiltration / substrate remodeling, and between ERK1 / 2 and EMT, autophagy, and cancer cell infiltration.
In addition, we elucidated the effect of the adipose stem cell-derived stromal cells on substrate density or pancreatic cancer invasion, and the effect of S100P expression in pancreatic cancer cells on the formation of single-layer circular defects in lymphatic vessels.

Academic Significance and Societal Importance of the Research Achievements

膵癌は、罹患者数と死亡者数がほぼ同数の極めて難治性の癌で、5年生存率は約7%と極めて予後不良な疾患であり、その診断法や治療法の新規開発は、社会的要請度・緊急性が高い。
本研究においては、細胞外マトリックスの新たなリモデリング機構としての脂肪幹細胞の働きや、膵癌細胞のリンパ管浸潤の機序などにも着目し、解析を重ねた。
それぞれにおいて基質リモデリングや上皮間葉転換などを介する癌細胞浸潤の抑制を誘導しうる有望な治療標的を各種同定するに至ったことは、膵癌治療に対する学術的、社会的要請に応じる結果が得られたといえる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer?stromal interaction and metastasis2019

    • Author(s)
      Yan Zilong、Ohuchida Kenoki、Fei Shuang、Zheng Biao、Guan Weiyu、Feng Haimin、Kibe Shin、Ando Yohei、Koikawa Kazuhiro、Abe Toshiya、Iwamoto Chika、Shindo Koji、Moriyama Taiki、Nakata Kohei、Miyasaka Yoshihiro、Ohtsuka Takao、Mizumoto Kazuhiro、Hashizume Makoto、Nakamura Masafumi
    • Journal Title

      Journal of Experimental & Clinical Cancer Research

      Volume: 38 Issue: 1 Pages: 221-221

    • DOI

      10.1186/s13046-019-1226-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer2019

    • Author(s)
      Nakayama H, Ohuchida K, Yonenaga A, Sagara A, Ando Y, Kibe S, Takesue S, Abe T, Endo S, Koikawa K, Okumura T, Shido K, Miyoshi K, Nakata K, Moriyama T, Miyasaka Y, Inoue S, Ohtsuka T, Mizumoto K, Nakamura M
    • Journal Title

      Int J Oncol

      Volume: 55 Pages: 211-222

    • DOI

      10.3892/ijo.2019.4812

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Basement membrane destruction by pancreatic stellate cells leads to local invasion in pancreatic ductal adenocarcinoma2018

    • Author(s)
      Koikawa K、Ohuchida K、Ando Y、Kibe S、Nakayama H、Takesue S、Endo S、Abe T、Okumura T、Iwamoto C、Moriyama T、Nakata K、Miyasaka Y、Ohtsuka T、Nagai E、Mizumoto K、Hashizume M、Nakamura M
    • Journal Title

      Cancer Letters

      Volume: 425 Pages: 65-77

    • DOI

      10.1016/j.canlet.2018.03.031

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix2018

    • Author(s)
      Okumura T, Ohuchida K, Kibe S, Iwamoto C, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Koikawa K, Sada M, Horioka K, Mochidome N, Arita M, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M
    • Journal Title

      Int J Cancer

      Volume: 144 Issue: 6 Pages: 1401-1413

    • DOI

      10.1002/ijc.31775

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo1802018

    • Author(s)
      Koikawa K, Ohuchida K, Takesue S, Ando Y, Kibe S, Nakayama H, Endo S, Abe T, Okumura T, Horioka K, Sada M, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Ohuchida R, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
    • Journal Title

      Cancer Letters

      Volume: 412 Pages: 143-154

    • DOI

      10.1016/j.canlet.2017.10.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵癌リンパ節転移におけるcollective cell invasion 制御因子の検討2019

    • Author(s)
      中山宏道、大内田研宙、安藤陽平、岐部晋、武居晋、進藤幸治、森山大樹、仲田興平、大塚隆生、中村雅史
    • Organizer
      第74回日本消化器外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] S100Pが癌細胞塊のリンパ管内皮層へのクリアランスに関与しリンパ節転移に関わる2019

    • Author(s)
      中山宏道、大内田研宙、相良亜希子、米永晃子、安藤陽平、岐部晋、武居晋、進藤幸治、仲田興平、森山大樹、宮坂義浩、藤田逸人、永井俊太郎、岡部安博、大塚隆生、水元一博、中村雅史
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Basement membrane destruction by pancreatic stellate cells leads to local invasion in pancreatic ductal adenocarcinoma2018

    • Author(s)
      Koikawa K, Ohuchida K, Ando Y, Kibe S, Nakayama H, Takesue S, Endo S, Abe T, Okumura T, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M
    • Organizer
      Pancreas 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] BM-derived cells differentiated into multilineage hematopoietic cells regulate invasion and proliferation of pancreatic cancer2018

    • Author(s)
      Iwamoto C, Ohuchida K, Okumura T, Koikawa K, Takesue S, Nakayama H, Endo S, Kibe S, Ando Y, Shindo K, Nakata K, Miyawaki K, Murata M, Akashi K, Nakamura M, Hashizume M
    • Organizer
      Pancreas 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fat tissue and pancreatic parenchyma play different roles in pancreatic cancer invasion2018

    • Author(s)
      Ohuchida K, Kibe S, Okumura T, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Nakamura M
    • Organizer
      Pancreas 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵星細胞が誘導する新たな膵癌局所微小浸潤機序の解明2017

    • Author(s)
      肥川和寛、大内田研宙、森山大樹、仲田興平、宮坂義浩、真鍋達也、大塚隆生、永井英司、水元一博、中村雅史
    • Organizer
      第25回日本消化器関連学会週間 第15回日本消化器外科学会大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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