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Expression and function of ADAM on cancer cell progression in human colorectal cancer

Research Project

Project/Area Number 18K07052
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionNational Defense Medical College

Principal Investigator

Mochizuki Satsuki  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 外科学, 助教 (80365428)

Co-Investigator(Kenkyū-buntansha) 上野 秀樹  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 外科学, 教授 (90597535)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsADAM / CAF / 線維性癌間質反応 / 大腸癌 / Desmoplastic reaction / オルガノイド / がん関連線維芽細胞 / ADAM / CAF / 癌間質 / 転移
Outline of Final Research Achievements

Desmoplastic reaction of colorectal cancer (CRC), i.e. Mature, Intermediate or Immature type, is related with prognosis, but molecular mechanism remains unknown. We demonstrate that survival rate is worst in Immature group, and secreted isoform of “a disintegrin and metalloproteinase-9” (ADAM9s) is overexpressed by cancer-associated fibroblasts from Immature-type CRC (CAFsImmature). CAFsImmature-derived ADAM9s contributes to increased proliferation and progression of CRC cells, suggesting the implications of CAFsImmature-derived ADAM9s for poor prognosis in CRC patients.

Academic Significance and Societal Importance of the Research Achievements

大腸癌細胞とCAFを区別してそれぞれで発現するADAM分子の情報や機能に関してはほとんど報告がない。一方、大腸癌浸潤先端部DRのimmatureタイプの形態学的特徴と予後との関連は当教室の上野秀樹教授らが独自に明らかにしたデータであるが、その形成機構やADAM分子の関与に関しては全く情報がない。これらのことから、本研究項目の遂行によって明らかにできるデータは、ADAMやCAFの研究分野に大きなインパクトを与えることができるばかりでなく、癌組織内微小環境研究分野に大きな貢献ができると期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2021 2020 2019 2018 Other

All Journal Article (17 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 17 results,  Open Access: 11 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Periostin as a key molecule defining desmoplastic environment in colorectal cancer2021

    • Author(s)
      Takahiro Sueyama , Yoshiki Kajiwara , Satsuki Mochizuki , Hideyuki Shimazaki , Eiji Shinto , Kazuo Hase , Hideki Ueno
    • Journal Title

      Virchows Arch

      Volume: 478 Issue: 5 Pages: 865-874

    • DOI

      10.1007/s00428-020-02965-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression and Function of a Disintegrin and Metalloproteinases in Cancer-Associated Fibroblasts of Colorectal Cancer2020

    • Author(s)
      Satsuki Mochizuki, Tadakazu Ao, Takumi Sugiura, Keisuke Yonemura、Takehiro Shiraishi、Yoshiki Kajiwara、Koichi Okamoto、Eiji Shinto、Yasunori Okada、Hideki Ueno
    • Journal Title

      Digestion

      Volume: 101 Issue: 1 Pages: 18-24

    • DOI

      10.1159/000504087

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Correlation Between Immunoinflammatory Measures and Periostin Expression in Esophageal Squamous Cell Carcinoma: A Single-Center, Retrospective Cohort Study2020

    • Author(s)
      Yusuke Ishibashi、Hironori Tsujimoto 、Takahiro Einama 、Satsuki Mochizuki、Keita Kouzu 、Shinsuke Nomura 、Nozomi Ito, Manabu Harada 、 Hidekazu Sugasawa 、 Eiji Shinto、 Yoji Kishi、 Hideki Ueno
    • Journal Title

      Annals of Surgical Oncology

      Volume: 28 Issue: 2 Pages: 1228-1237

    • DOI

      10.1245/s10434-020-08765-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphological consistency of desmoplastic reactions between the primary colorectal cancer lesion and associated metastatic lesions2020

    • Author(s)
      Tadakazu Ao , Yoshiki Kajiwara , Keisuke Yonemura , Eiji Shinto , Satsuki Mochizuki , Koichi Okamoto , Yoji Kishi , Hideki Ueno
    • Journal Title

      Virchows Arch

      Volume: 477 Issue: 1 Pages: 47-55

    • DOI

      10.1007/s00428-019-02742-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Primary Tumor Histology Affects Oncological Outcomes Independently of the Anatomical Extent of Disease in Colorectal Liver Metastasis2020

    • Author(s)
      Hideki Ueno , Tsuyoshi Konishi , Yuichi Ishikawa , Hideyuki Shimazaki , Masashi Ueno , Suefumi Aosasa , Akio Saiura , Eiji Shinto , Yoshiki Kajiwara , Satsuki Mochizuki , Takahiro Nakamura , Junji Yamamoto
    • Journal Title

      JMA Journal

      Volume: 3 Issue: 3 Pages: 240-250

    • DOI

      10.31662/jmaj.2018-0004

    • NAID

      130007905812

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Systemic steroid treatment can desensitize the skin reaction due to regorafenib in a recurrence colorectal cancer patient2019

    • Author(s)
      Tashiro Keita、Shinto Eiji、Kajiwara Yoshiki、Mochizuki Satsuki、Okamoto Koichi、Nishizawa Aya、Satoh Takahiro、Kishi Yoji、Ueno Hideki
    • Journal Title

      International Cancer Conference Journal

      Volume: 8 Issue: 4 Pages: 164-169

    • DOI

      10.1007/s13691-019-00376-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential clinical impacts of tumour budding evaluated by immunohistochemical and haematoxylin and eosin staining in stage II colorectal cancer.2019

    • Author(s)
      Masato Yamadera, Eiji Shinto, Yoshiki Kajiwara, Satsuki Mochizuki, Koichi Okamoto, Hideyuki Shimazaki, Kazuo Hase, Hideki Ueno
    • Journal Title

      Histopathology

      Volume: 印刷中 Issue: 7 Pages: 1005-1013

    • DOI

      10.1111/his.13830

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential Survival Benefits of 5-Fluorouracil Based Adjuvant Chemotherapy for Patients With Microsatellite-Stable Stage III Colorectal Cancer According to the Tumor Budding Status2019

    • Author(s)
      Yamadera Masato、Shinto Eiji、Kajiwara Yoshiki、Mochizuki Satsuki、Okamoto Koichi、Hase Kazuo、Yamamoto Junji、Ueno Hideki
    • Journal Title

      Diseases of the Colon & Rectum

      Volume: 62 Issue: 11 Pages: 1316-1325

    • DOI

      10.1097/dcr.0000000000001480

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Multicenter Study of the Prognostic Value of Desmoplastic Reaction Categorization in Stage II Colorectal Cancer2019

    • Author(s)
      Ueno Hideki、Kanemitsu Yukihide、Sekine Shigeki、Ishiguro Megumi、Ito Eisaku、Hashiguchi Yojiro、Kondo Fukuo、Shimazaki Hideyuki、Kajiwara Yoshiki、Okamoto Koichi、Mochizuki Satsuki、Tsujimoto Hironori、Shinto Eiji
    • Journal Title

      The American Journal of Surgical Pathology

      Volume: 43 Issue: 8 Pages: 1015-1022

    • DOI

      10.1097/pas.0000000000001272

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic significance of histological categorization of desmoplastic reaction in colorectal liver metastases2019

    • Author(s)
      Ao Tadakazu、Kajiwara Yoshiki、Yonemura Keisuke、Shinto Eiji、Mochizuki Satsuki、Okamoto Koichi、Aosasa Suefumi、Ueno Hideki
    • Journal Title

      Virchows Archiv

      Volume: 475 Issue: 3 Pages: 341-348

    • DOI

      10.1007/s00428-019-02580-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel Internationally Verified Method Reports Desmoplastic Reaction as the Most Significant Prognostic Feature For Disease-specific Survival in Stage II Colorectal Cancer2019

    • Author(s)
      Nearchou Ines P.、Kajiwara Yoshiki、Mochizuki Satsuki、Harrison David J.、Caie Peter D.、Ueno Hideki
    • Journal Title

      The American Journal of Surgical Pathology

      Volume: 43 Issue: 9 Pages: 1239-1248

    • DOI

      10.1097/pas.0000000000001304

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic Value of Poorly Differentiated Clusters in Liver Metastatic Lesions of Colorectal Carcinoma2019

    • Author(s)
      Yonemura Keisuke、Kajiwara Yoshiki、Ao Tadakazu、Mochizuki Satsuki、Shinto Eiji、Okamoto Koichi、Hase Kazuo、Ueno Hideki
    • Journal Title

      The American Journal of Surgical Pathology

      Volume: 43 Issue: 10 Pages: 1341-1348

    • DOI

      10.1097/pas.0000000000001329

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesothelin expression has prognostic value in stage ΙΙ/ΙΙΙ colorectal cancer.2019

    • Author(s)
      Takehiro Shiraishi, Eiji Shinto, Satsuki Mochizuki, Hitoshi Tsuda, Yoshiki Kajiwara, Koichi Okamoto, Takahiro Einama, Kazuo Hase, Hideki Ueno
    • Journal Title

      Virchows Arch

      Volume: 474 Issue: 3 Pages: 297-307

    • DOI

      10.1007/s00428-018-02514-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cancer-induced spiculation on computed tomography: a significant preoperative prognostic factor for colorectal cancer.2019

    • Author(s)
      Tadakazu Ao, Yoshiki Kajiwara, Yamada K3, Eiji Shinto, Satsuki Mochizuki, Koichi Okamoto, Masato Yamadera, Keisuke Yonemura, Hideki Ueno
    • Journal Title

      Surg. Today

      Volume: 印刷中 Issue: 7 Pages: 629-636

    • DOI

      10.1007/s00595-019-01780-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Selective inhibition of ADAM28 suppresses lung carcinoma cell growth and metastasis2018

    • Author(s)
      Satsuki Mochizuki, Masayuki Shimoda, Hitoshi Abe, Yuka Miyamae, Junko Kuramoto, Noriko Aramaki-Hattori, Ken Ishii, Hideki Ueno, Akira Miyakoshi, Kanehisa Kojoh and Yasunoti Okada
    • Journal Title

      Mol. Cancer Ther

      Volume: 17 Issue: 11 Pages: 2427-2438

    • DOI

      10.1158/1535-7163.mct-17-1198

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Is Up-Regulated and Involved in Hyaluronan Degradation in Human Osteoarthritic Cartilage.2018

    • Author(s)
      Shimizu H, Shimoda M, Mochizuki S, Miyamae Y, Abe H, Chijiiwa M, Yoshida H, Shiozawa J, Ishijima M, Kaneko K, Kanaji A, Nakamura M, Toyama Y, Okada Y.
    • Journal Title

      Am J Pathol.

      Volume: 188 Issue: 9 Pages: 2109-2119

    • DOI

      10.1016/j.ajpath.2018.05.012

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SOX4, an epithelial-mesenchymal transition inducer, transactivates ADAM28 gene expression and co-localizes with ADAM28 at the invasive front of human breast and lung carcinomas2018

    • Author(s)
      Aya Sasaki, Hitoshi Abe, Satsuki Mochizuki, Masayuki Shimoda and Yasunori Okada
    • Journal Title

      Pathol Int.

      Volume: - Issue: 8 Pages: 449-458

    • DOI

      10.1111/pin.12685

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] がん関連線維芽細胞で発現するADAM分子による線維性癌間質反応への関与2019

    • Author(s)
      望月早月、阿尾理一、梶原由規、米村圭介、岡本耕一、神藤英二、下田将之、長谷和生、上野秀樹
    • Organizer
      第15回日本消化管学会総会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of human antibody against ADAM28, a key modulator of tumor microenvironmental factors in non-small cell lung carcinomas.2018

    • Author(s)
      Satsuki Mochizuki , Masayuki Shimoda, Hideki Ueno and Yasunori Okada
    • Organizer
      Matrix Biology Europe 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 医学のあゆみ「線維症とメタロプロテアーゼーMMP・ADAM・ADAMTS」2020

    • Author(s)
      望月早月、岡田保典
    • Publisher
      医師薬出版
    • Related Report
      2020 Annual Research Report
  • [Remarks] 防衛医科大学校 外科学(消化管外科)

    • URL

      http://www.ndmc.ac.jp/med/subject/sh_med039%e5%a4%96%e7%a7%91%e5%ad%a6%ef%bc%88%e6%b6%88%e5%8c%96%e7%ae%a1%e5%a4%96%e7%a7%91%ef%bc%89/

    • Related Report
      2019 Research-status Report
  • [Remarks] 防衛医科大学外科学(消化管外科)

    • URL

      http://www.ndmc.ac.jp/med/subject/sh_med038syoukakangeka/

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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