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Analysis of the interaction between the folate receptor beta expression macrophages and cancer stem cells in pancreatic cancer invasion

Research Project

Project/Area Number 25293288
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

TAKAO SONSHIN  鹿児島大学, 医用ミニブタ・先端医療開発研究センター, 特任教授 (80171411)

Co-Investigator(Kenkyū-buntansha) MATSUYAMA TAKAMI  鹿児島大学, 医用ミニブタ先端医療開発研究センター, 客員教授 (30145479)
Matsubara Shyichiro  鹿児島大学, 医用ミニブタ先端医療開発研究センター, 准教授 (60199841)
NAGAI TAKU  鹿児島大学, 医歯学域医学系, 講師 (90363647)
DING QIANG  聖ミカエル病院李嘉誠知識研究所, キーナン研究センター (80457647)
YOSHIMITSU MAKOTO  鹿児島大学, 医歯学域医学系, 准教授 (70404530)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywordspancreatic cancer / cancer stem cell / CD133 / macrophage / FRb-receptor / tumor microenvironment / miR-30 / FRbeta / microRNA / invasion / migration / FRb receptor / fibrotic stroma / nude mouse / EMT / N-cadherin / miRNA / caerulein誘導慢性膵炎 / FRβマクロファージ / CD68マクロファージ / ヒト化抗FRαβ抗体
Outline of Final Research Achievements

In this study, we examine the relevance to the invasion of pancreatic fibrosis and cancer stem cells. CD133 expression pancreatic cancer cells showing the cancer stem cell-like characteristics showed fibrosis enhancement and high expression of active macrophages interstitial in the pancreas within the transplantation of immunocompromised mice. Many of the active macrophages were present in the invasion site express FRβ. To establish a blood soluble FRβ measurement system, a result of the study the correlation between the clinical data of pancreatic cancer 20 cases, serum soluble FRβ high-value group has a high possibility of lymph node metastasis, clinical application has been suggested. In addition, CD133 expression pancreatic cancer cells were significantly enhanced the hematogenous metastases through the expression of EMT-related genes. It was further found that the miR-30 family plays an important role in the invasion of CD133 expression pancreatic cancer cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (20 results)

All 2016 2015 2014 2013 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (14 results)

  • [Journal Article] miR-30 family promotes migratory and invasive abilities in CD133+ pancreatic cancer stem-like cells.2016

    • Author(s)
      Tsukasa K, Ding Q, Miyazaki Y, Matsubara S, Natsugoe S, Takao S.
    • Journal Title

      Hum Cell

      Volume: 0 Pages: 0-0

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Production of a High-affinity Monoclonal Antibody Reactive with Folate Receptors Alpha and Beta.2015

    • Author(s)
      Nagai T, Furusho Y, Li H, Hasui K, Matsukita S, Sueyoshi K, Yanagi M, Hatae M, Takao S, Matsuyama T.
    • Journal Title

      Monoclon Antib Immunodiagn Immunother.

      Volume: 34 Issue: 3 Pages: 181-190

    • DOI

      10.1089/mab.2014.0072

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Depletion of folate receptor β-expressing macrophages alleviates bleomycin-induced experimental skin fibrosis2014

    • Author(s)
      Li H, Nagai T, Hasui K, Matsuyama T.
    • Journal Title

      Mod Rheumatol

      Volume: - Issue: 5 Pages: 816-822

    • DOI

      10.3109/14397595.2013.879415

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage uptake and accumulation of folates are polarization-dependent in vitro and in vivo and are regulated by activin A.2014

    • Author(s)
      Samaniego R, Palacios BS, Domiguez-Soto A, Vidal C, Salas A, Matsuyama T, Sánchez-Torres C, de la Torre I, Miranda-Carús ME, Sánchez-Mateos P, Puig-Kröger A.
    • Journal Title

      Journal of Leukocyte Biology

      Volume: 95 Issue: 5 Pages: 797-808

    • DOI

      10.1189/jlb.0613345

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD133 facilitates epithelial-mesenchymal transition through interaction with the ERK pathway in pancreatic cancer metastasis.2014

    • Author(s)
      Ding Q, Miyazaki Y, Tsukasa K, Matsubara S, Yoshimitsu M, Takao S.
    • Journal Title

      Molecular Cancer

      Volume: 13 Issue: 1

    • DOI

      10.1186/1476-4598-13-15

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mTOR plays critical roles in pancreatic cancer stem cells through specific and stemness-related functions.2013

    • Author(s)
      Matsubara S, Ding Q, Miyazaki Y, Kuwahata T, Tsukasa K and Takao S
    • Journal Title

      Scientific Report

      Volume: 3 Issue: 1

    • DOI

      10.1038/srep03230

    • NAID

      120005672468

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] The influence of miR-30 family to migration of a pancreatic cancer cell line, Capan-1.2015

    • Author(s)
      Koichiro Tsukasa, Shoko Ueno, Yumi Miyazaki, Toru Obara, Shyichiro Matsubara, Sonshin Takao
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-10-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Slug contributes to gemcitabine resistance through epithelial-mesenchymal transition in CD133+ pancreatic cancer cells.2015

    • Author(s)
      Koichiro Tsukasa, Qiang Ding, Makoto Yoshimitsu, Yumi Miyazaki, Shyuichiro Matsubara, Shoko Ueno, Toru Obara , Takami Matsuyama, Sonshin Takao
    • Organizer
      第33回ヒト細胞学会学術集会
    • Place of Presentation
      宮崎市
    • Year and Date
      2015-08-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膵癌幹細胞とKRAS – mTOR経路2015

    • Author(s)
      松原 修一郎、政 幸一郎、宮崎 優美、小原 徹、高尾 尊身
    • Organizer
      第4回鹿児島膵勉強会
    • Place of Presentation
      ブルーウェーブイン鹿児島(鹿児島県鹿児島市)
    • Year and Date
      2015-03-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] The role of miR-30a in the highly migratory pancreatic cancer cell line.2014

    • Author(s)
      Koichiro Tsukasa, Qiang Ding, Ryoko Imakiire, Shoko Ueno, Yumi Miyazaki, Toru Obara, Shyichiro Matsubara, Sonshin Takao
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      国際会議場(神奈川県横浜市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Not only mTORC1 but also mTORC2 are involved in the function to maintain stem-like property of pancreatic cancer cells.2014

    • Author(s)
      Matsubara S, Miyazaki Y, Tsukasa K, Obara T, Ueno S, Takao S
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      国際会議場(神奈川県横浜市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] The roles of novel tumor-associated macrophages (TAMs) in invasion and metastasis of pancreatic cancer

    • Author(s)
      Sonshin Takao, Qiang Ding, Taku Nagai, Hiroshi Kurahara, Makoto Yoshimitsu, Taisaku Kuwahata, Yumi Miyazaki, Ryoko Imakiire, Shoko Ueno, Toru Obara, Takami Matsuyama
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of Slug in chemoresistance, invasion and metastasis of CD133-expressing pancreatic cancer

    • Author(s)
      Koichirou Tsukasa, Qiang Ding, Makoto Yoshimitsu, Yumi Miyazaki, Toru Obara, Shyuichiro Matsubara, Sonshin Takao
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] GLI-1 plays a pivotal role in Hedgehog pathway on self-renewal of pancreatic cancer stem cells

    • Author(s)
      Yumi Miyazaki, Qiang Ding, Makoto Yoshimitsu, Toru Obara, Koichirou Tsukasa, Shyuichiro Matsubara, Sonshin Takao
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] CD133/ERK axis mediates invasion and metastasis through epithelial-to-mesenchymal transition (EMT) in pancreatic cancer

    • Author(s)
      Qiang Ding, Makoto Yoshimitsu, Koichiro Tsukasa, Yumi Miyazaki, Shoko Ueno, Ryoko Imakiire, Toru Obara and Sonshin Takao
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Immunohistochemical comparative analysis of the sphere cells of CD133-positive pancreatic cancer cells with iPS cells

    • Author(s)
      Yumi Miyazaki, Wang Yuqing, Kaoru Mitsui, Qiang Ding, Koichiro Tsukasa, Shyuichiro Matsubara, Kenichiro Kosai and Sonshin Takao
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] The mTOR pathway as a mechanism to maintain pancreatic cancer stem cell properties and a target to eliminate stem-like cells

    • Author(s)
      Shyuichiro Matsubara, Qiang Ding, Yumi Miyazaki, Taisaku Kuwahata, Koichiro Tsukasa and Sonshin Takao
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Efficacy of an antibody reactive with human folate receptors a and b in targeting cancer cells and TAMs

    • Author(s)
      Nagai T, Hasui K, Matsuyama T, Takao S, Hatae M, Sueyoshi K, Matsukida S
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] CD133 facilitates pancreatic cancer metastasis by promoting epithelial-mesenchymal transition (EMT)

    • Author(s)
      Qiang Ding, Makoto Yoshimitsu, Yumi Miyazaki, Toru Obara, Koichirou Tsukasa, Shyuichiro Matsubara, Sonshin Takao
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] The role of noncoding RNAs in highly CD133-expressing pancreatic cancer stem-like cells

    • Author(s)
      Koichiro Tsukasa, Qiang Ding, Ryoko Imakiire, Shoko Ueno, Yumi Miyazaki, Toru Obara, Shyichiro Matsubara, Sonshin Takao
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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