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Molecular dissection of angiogenesis in colorectal cancer

Research Project

Project/Area Number 18K07949
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionSapporo Medical University

Principal Investigator

Yamamoto Eiichiro  札幌医科大学, 医学部, 訪問研究員 (60567915)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords大腸がん / 微小環境 / がん微小環境 / 腫瘍血管 / がん間質 / 遺伝子発現
Outline of Final Research Achievements

We detected frequent upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in TECs. Immunohistochemistry revealed that AEBP1 is upregulated TECs and cancer stromal cells. Levels of AEBP1 expression in human umbilical vein endothelial cells (HUVECs) were upregulated by tumor conditioned medium derived from CRC cells or by direct co-culture with CRC cells. AEBP1 knockdown suppressed proliferation, migration and in vitro tube formation by HUVECs. In xenograft experiments, AEBP1 knockdown suppressed tumorigenesis and microvessel formation. Depletion of AEBP1 in HUVECs downregulated a series of genes associated with angiogenesis, including aquaporin 1 (AQP1) and periostin (POSTN), suggesting that AEBP1 may promote angiogenesis through regulating those genes. These results suggest that upregulation of AEBP1 contributes to tumor angiogenesis in CRC, which makes AEBP1 a potentially useful therapeutic target.

Academic Significance and Societal Importance of the Research Achievements

腫瘍間質は、がん関連線維芽細胞、腫瘍血管内皮細胞(tumor endothelial cell, TEC)、種々の免疫細胞などから構成されている。腫瘍間質細胞はがんの増殖、浸潤および転移に有利な微小環境を構築することから、その制御は重要な治療戦略である。本研究でAEBP1 (adipocyte enhancer-binding protein 1) がTECで高発現し、血管新生を促進すること、そしてAEBP1の阻害が腫瘍血管新生を抑制しうることを明らかとしており、今後がん微小環境におけるAEBP1の機能を解明することで、新たな分子標的治療法の開発につなげることができると考えられた。

Report

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

    (19 results)

All 2021 2020 2019 2018

All Journal Article (18 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 18 results,  Open Access: 15 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The continuum of transformation of TSA to low‐grade neoplasia and cancer with BRAF mutation ? A case with molecular analysis2021

    • Author(s)
      Aoki Hironori、Adachi Yasushi、Yamamoto Eiichiro、Yoshida Yukinari、Ishii Yoshifumi、Yamano Hiro‐o、Suzuki Hiromu、Endo Takao
    • Journal Title

      Pathology International

      Volume: - Issue: 5 Pages: 368-370

    • DOI

      10.1111/pin.13078

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual EZH2 and G9a inhibition suppresses multiple myeloma cell proliferation by regulating the interferon signal and IRF4-MYC axis.2021

    • Author(s)
      Ishiguro K, Kitajima H, Niinuma T, Maruyama R, Nishiyama N, Ohtani H, Sudo G, Toyota M, Sasaki H, Yamamoto E, Kai M, Nakase H, Suzuki H.
    • Journal Title

      Cell Death Discovery

      Volume: 7 Issue: 1 Pages: 7-7

    • DOI

      10.1038/s41420-020-00400-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulation of AEBP1 in endothelial cells promotes tumor angiogenesis in colorectal cancer2020

    • Author(s)
      Yorozu Akira、Yamamoto Eiichiro、Niinuma Takeshi、Tsuyada Akihiro、Maruyama Reo、Kitajima Hiroshi、Numata Yuto、Kai Masahiro、Sudo Gota、Kubo Toshiyuki、Nishidate Toshihiko、Okita Kenji、Takemasa Ichiro、Nakase Hiroshi、Sugai Tamotsu、Takano Kenichi、Suzuki Hiromu
    • Journal Title

      Cancer Science

      Volume: - Issue: 5 Pages: 1631-1644

    • DOI

      10.1111/cas.14360

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of gene mutations in the Wnt signaling pathway in traditional serrated adenomas of the colon and rectum2020

    • Author(s)
      Nakanishi, H. Sawada, T. Kaizaki, Y. Ota, R. Suzuki, H. Yamamoto, E. Aoki, H. Eizuka, M. Hasatani, K. Takahashi, N. Inagaki, S. Ebi, M. Kato, H. Kubota, E. Kataoka, H. Takahashi, S. Tokino, T. Minamoto, T. Sugai, T. Sasaki, Y.
    • Journal Title

      PLoS One

      Volume: 15 Issue: 2 Pages: e0229262-e0229262

    • DOI

      10.1371/journal.pone.0229262

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrated genetic and epigenetic analysis of cancer‐related genes in non‐ampullary duodenal adenomas and intramucosal adenocarcinomas2020

    • Author(s)
      Ota R、Sawada T、Tsuyama S、Sasaki Y、Suzuki H、Kaizaki Y、Hasatani K、Yamamoto E、Nakanishi H、Inagaki S、Tsuji S、Yoshida N、Doyama H、Minato H、Nakamura K、Kasashima S、Kubota E、Kataoka H、Tokino T、Yao T、Minamoto T
    • Journal Title

      The Journal of Pathology

      Volume: 252 Issue: 3 Pages: 330-342

    • DOI

      10.1002/path.5529

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular biology of colorectal cancer -mechanism of tumorigenesis and molecular subtypes-2019

    • Author(s)
      鈴木 拓、山本 英一郎、仲瀬 裕志
    • Journal Title

      Nippon Shokakibyo Gakkai Zasshi

      Volume: 116 Issue: 11 Pages: 859-866

    • DOI

      10.11405/nisshoshi.116.859

    • NAID

      130007743552

    • ISSN
      0446-6586, 1349-7693
    • Year and Date
      2019-11-10
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sessile serrated adenoma/polyp showed rapid malignant transformation in the final 13?months2019

    • Author(s)
      Amemori Sadahiro、Yamano Hiro‐o、Tanaka Yoshihito、Yoshikawa Kenjiro、Matsushita Hiro‐o、Takagi Ryo、Harada Eiji、Yoshida Yuko、Tsuda Kazunori、Kato Bunichiro、Tamura Eri、Eizuka Makoto、Sugai Tamotsu、Adachi Yasushi、Yamamoto Eiichiro、Suzuki Hiromu、Nakase Hiroshi
    • Journal Title

      Digestive Endoscopy

      Volume: - Issue: 6 Pages: 979-983

    • DOI

      10.1111/den.13572

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] UHRF1 depletion and HDAC inhibition reactivate epigenetically silenced genes in colorectal cancer cells2019

    • Author(s)
      Niinuma Takeshi、Kitajima Hiroshi、Kai Masahiro、Yamamoto Eiichiro、Yorozu Akira、Ishiguro Kazuya、Sasaki Hajime、Sudo Gota、Toyota Mutsumi、Hatahira Tomo、Maruyama Reo、Tokino Takashi、Nakase Hiroshi、Sugai Tamotsu、Suzuki Hiromu
    • Journal Title

      Clinical Epigenetics

      Volume: 11 Issue: 1 Pages: 70-70

    • DOI

      10.1186/s13148-019-0668-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis.2019

    • Author(s)
      Suzuki H, Yamamoto E, Yamano HO, Nakase H, Sugai T.
    • Journal Title

      Digestion.

      Volume: 99 Issue: 1 Pages: 33-38

    • DOI

      10.1159/000494410

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DOT1L inhibition blocks multiple myeloma cell proliferation by suppressing IRF4-MYC signaling2018

    • Author(s)
      Ishiguro Kazuya、Kitajima Hiroshi、Niinuma Takeshi、Ishida Tadao、Maruyama Reo、Ikeda Hiroshi、Hayashi Toshiaki、Sasaki Hajime、Wakasugi Hideki、Nishiyama Koyo、Shindo Tetsuya、Yamamoto Eiichiro、Kai Masahiro、Sasaki Yasushi、Tokino Takashi、Nakase Hiroshi、Suzuki Hiromu
    • Journal Title

      Haematologica

      Volume: 104 Issue: 1 Pages: 155-165

    • DOI

      10.3324/haematol.2018.191262

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the expression of cancer-associated fibroblast- and EMT-related proteins in submucosal invasive colorectal cancer.2018

    • Author(s)
      Sugai T, Uesugi N, Kitada Y, Yamada N, Osakabe M, Eizuka M, Sugimoto R, Fujita Y, Kawasaki K, Yamamoto E, Yamano H, Suzuki H, Matsumoto T.
    • Journal Title

      J Cancer.

      Volume: 9 Issue: 15 Pages: 2702-2712

    • DOI

      10.7150/jca.25646

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU12018

    • Author(s)
      Nishiyama K、Maruyama R、Niinuma T、Kai M、Kitajima H、Toyota M、Hatanaka Y、Igarashi T、Kobayashi J、Ogi K、Dehari H、Miyazaki A、Yorozu A、Yamamoto E、Idogawa M、Sasaki Y、Sugai T、Tokino Takashi、Hiratsuka H、Suzuki H
    • Journal Title

      Cell Death & Disease

      Volume: 9 Issue: 8 Pages: 826-826

    • DOI

      10.1038/s41419-018-0893-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment2018

    • Author(s)
      Wakasugi H, Takahashi H, Niinuma T, Kitajima H, Oikawa R, Matsumoto N, Takeba Y, Otsubo T, Takagi M, Ariizumi Y, Suzuki M, Okuse C, Iwabuchi S, Nakano M, Akutsu N, Kang JH, Matsui T, Yamada N, Sasaki H, Yamamoto E, Kai M, Sasaki Y, Sasaki, Tanaka, Yotsuyanagi, Tsutsumi, Yamamoto, Tokino T , Nakase H, Suzuki H, Itoh F
    • Journal Title

      Cancer Letters

      Volume: 434 Pages: 91-100

    • DOI

      10.1016/j.canlet.2018.07.019

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions.2018

    • Author(s)
      Sugai T, Eizuka M, Fujita Y, Kawasaki K, Yamamoto E, Ishida K, Yamano H, Suzuki H, Matsumoto T.
    • Journal Title

      Dig Dis Sci.

      Volume: 63 Issue: 10 Pages: 2626-2638

    • DOI

      10.1007/s10620-018-5167-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surface microstructures are associated with mutational intratumoral heterogeneity in colorectal tumors2018

    • Author(s)
      Harada T、Yamamoto E、Yamano HO、Aoki H、Matsushita HO、Yoshikawa K、Takagi R、Harada E、Tanaka Y、Yoshida Y、Eizuka M、Yorozu A、Sudo G、Kitajima H、Niinuma T、Kai M、Sasaki Y、Tokino Takashi、Sugai T、Nakase H、Suzuki H
    • Journal Title

      Journal of Gastroenterology

      Volume: 53 Issue: 12 Pages: 1241-1252

    • DOI

      10.1007/s00535-018-1481-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive molecular analysis based on somatic copy number alterations in intramucosal colorectal neoplasias and early invasive colorectal cancers.2018

    • Author(s)
      Sugai T, Eizuka M, Habano W, Fujita Y, Sato A, Sugimoto R, Otsuka K, Yamamoto E, Matsumoto T, Suzuki H.
    • Journal Title

      Oncotarget.

      Volume: 9 Issue: 33 Pages: 22895-22906

    • DOI

      10.18632/oncotarget.25112

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.2018

    • Author(s)
      Aoki H, Yamamoto E, Yamano HO, Sugai T, Kimura T, Tanaka Y, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Nakaoka M, Yoshida Y, Harada T, Sudo G, Eizuka M, Yorozu A, Kitajima H, Niinuma T, Kai M, Nojima M, Suzuki H, Nakase H.
    • Journal Title

      Dig Dis Sci.

      Volume: 15 Issue: 7 Pages: 1920-1928

    • DOI

      10.1007/s10620-018-5016-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular profiling and comprehensive genome-wide analysis of somatic copy number alterations in gastric intramucosal neoplasias based on microsatellite status.2018

    • Author(s)
      Sugai T, Eizuka M, Arakawa N, Osakabe M, Habano W, Fujita Y, Yamamoto E, Yamano H, Endoh M, Matsumoto T, Suzuki H.
    • Journal Title

      Gastric Cancer.

      Volume: 21 Issue: 5 Pages: 765-775

    • DOI

      10.1007/s10120-018-0810-5

    • NAID

      40021642313

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Patent(Industrial Property Rights)] がん微小環境を制御する治療剤2018

    • Inventor(s)
      山本 英一郎、鈴木 拓、萬 顕、菅井 有
    • Industrial Property Rights Holder
      山本 英一郎、鈴木 拓、萬 顕、菅井 有
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-146981
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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

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