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Expression of annexin II and stromal tenascin C promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer

Research Project

Project/Area Number 16K15607
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionChiba University

Principal Investigator

Takano Shigetsugu  千葉大学, 大学院医学研究院, 助教 (20436380)

Co-Investigator(Kenkyū-buntansha) 佐藤 守  千葉大学, 医学部附属病院, 特任准教授 (20401002)
吉富 秀幸  千葉大学, 大学院医学研究院, 准教授 (60375631)
宮崎 勝  国際医療福祉大学, 大学病院, 教授 (70166156)
酒井 望  千葉大学, 医学部附属病院, 助教 (70436385)
賀川 真吾  千葉大学, 医学部附属病院, 助教 (90507302)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords膵癌 / Annexin II / Tenascin C / 癌細胞ー間質相互作用 / 浸潤 / 転移 / 膵臓外科学 / 浸潤・転移 / 癌
Outline of Final Research Achievements

The interaction of cancer cells and stromal components contributes to cancer progression. We explored the correlation of annexin II (ANX2) and stromal tenascin C (TNC) with pancreatic cancer (PDAC) progression. In ANX2 knockdown cells, there were fewer cells with a mesenchymal appearance in 3D culture and reduced invasion. Morphological change into mesenchymal phenotype and invasion were enhanced more by recombinant TNC treatment in control cells but not in ANX2 knockdown cells. Pancreatosphere formation assays showed that both ANX2 and TNC facilitated stem-like characters, and anoikis assays indicated that the ANX2-TNC interaction contributes to anoikis resistance in PDAC cells. In IHC analyses, the ANX2 High/stromal TNC High expression group showed a significant correlation with distant metastasis and poor outcomes after surgery. In conclusion, ANX2 and stromal TNC regulate invasion along with stemness and anoikis resistance, which are crucial for metastasis in PDAC progression.

Academic Significance and Societal Importance of the Research Achievements

膵癌は最も予後不良な癌であり、5年生存率は未だ10%に満たない疾患である。その最大の理由の1つとして挙げられるのは、膵癌自体の悪性度の高さ(浸潤・転移能)と考えられる。本研究でAnnexin-IIとTenascin Cによる、癌細胞と癌周囲微小環境の相互作用について明らかとなったことで、膵癌進展機序の解明および今後の新規治療開発につながる研究成果と考えられる。本研究の内容については2018年 International Journal of Molecular Medicineに受理され、論文報告された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (3 results)

  • [Journal Article] Roles of Pin1 as a Key Molecule for EMT Induction by Activation of STAT3 and NF-κB in Human Gallbladder Cancer2019

    • Author(s)
      Nakada S, Kuboki S, Nojima H, Yoshitomi H, Furukawa K, Takayashiki T, Takano S, Miyazaki M, Ohtsuka M.
    • Journal Title

      Ann Surg Oncol.

      Volume: 26 Issue: 3 Pages: 907

    • DOI

      10.1245/s10434-018-07132-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of annexin II and stromal tenascin C promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer.2018

    • Author(s)
      Yoneura N, Takano S, Yoshitomi H, Nakata Y, Shimazaki R, Kagawa S, Furukawa K, Takayashiki T, Kuboki S, Miyazaki M, Ohtsuka M.
    • Journal Title

      Int J Mol Med.

      Volume: 42 Pages: 821-830

    • DOI

      10.3892/ijmm.2018.3652

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conversion surgery with gemcitabine plus nab-paclitaxel for locally advanced unresectable pancreatic cancer: A case report.2018

    • Author(s)
      Okura R, Takano S, Yokota T, Yoshitomi H, Kagawa S, Furukawa K, Takayashiki T, Kuboki S, Suzuki D, Sakai N, Nojima H, Mishima T, Miyazaki M, Ohtsuka M.
    • Journal Title

      Mol Clin Oncol.

      Volume: 9 Pages: 389-393

    • DOI

      10.3892/mco.2018.1688

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Annexin II and stromal tenascin C expression promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer2018

    • Author(s)
      Naoko Yoneura, Shigetsugu Takano*, Hideyuki Yoshitomi, Yasuyuki Nakata, Reiri Shimazaki, Shingo Kagawa, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Masaru Miyazaki, Masayuki Ohtsuka
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer2017

    • Author(s)
      Satoh M, Takano S, Sogawa K, Noda K, Yoshitomi H, Ishibashi M, Mogushi K, Takizawa H, Otsuka M, Shimizu H, Miyazaki M, Nomura F.
    • Journal Title

      Cancer Sci.

      Volume: 108 Issue: 4 Pages: 795

    • DOI

      10.1111/cas.13181

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags2016

    • Author(s)
      Sogawa K, Takano S, Iida F, Satoh M, Tsuchida S, Kawashima Y, Yoshitomi H, Sanda A, Kodera Y, Takizawa H, Mikata R, Ohtsuka M, Shimizu H, Miyazaki M, Yokosuka O, Nomura F.
    • Journal Title

      Br J Cancer.

      Volume: 115 Issue: 8 Pages: 949

    • DOI

      10.1038/bjc.2016.295

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] ETS-Transcription Factor ETV1 Regulates Stromal Expansion and Metastasis in Pancreatic Cancer.2016

    • Author(s)
      Heeg S, Das KK, Reichert M, Bakir B, Takano S, Caspers J, Aiello NM, Wu K, Neesse A, Maitra A, Iacobuzio-Donahue CA, Hicks P, Rustgi AK.
    • Journal Title

      Gastroenterology.

      Volume: 151 Issue: 3 Pages: 540-553

    • DOI

      10.1053/j.gastro.2016.06.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Prrx1 isoform switching regulates pancreatic cancer invasion and metastatic colonization2016

    • Author(s)
      Shigetsugu Takano, Maximilian Reichert, Basil Bakir, Koushik K. Das, Takahiro Nishida, Masaru Miyazaki, Steffen Heeg, Meredith A. Collins, Benoît Marchand, Philip D. Hicks, Anirban Maitra, and Anil K. Rustgi
    • Journal Title

      GENES & DEVELOPMENT

      Volume: 30 Issue: 2 Pages: 233-247

    • DOI

      10.1101/gad.263327.115

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Annexin II plays diverse functions during pancreatic cancer progression2018

    • Author(s)
      Shigetsugu Takano, Shingo Kagawa, Naoko Yoneura, Hideyuki Yoshitomi, Fumio Nomura*, Masayuki Ohtsuka
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Annexin II発現による抗癌剤耐性、および癌-間質細胞間相互作用による浸潤転移機構の解明2017

    • Author(s)
      米浦直子、高野重紹、賀川真吾、吉富秀幸、古川勝規、高屋敷吏、 久保木知、鈴木大亮、酒井 望、野島広之、大塚将之
    • Organizer
      日本がん転移学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Annexin II発現における膵癌バイオマーカーの臨床学的意義2016

    • Author(s)
      高野重紹、吉富秀幸、賀川真吾、清水宏明、大塚将之、加藤厚、古川勝規、高屋敷吏、久保木知、鈴木大亮、酒井望、野島広之、宮崎勝
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪国際会議場/リーガロイヤルホテル大阪(大阪府大阪市)
    • Year and Date
      2016-04-14
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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