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Roles of tumor invasion marker laminin gamma2 chain in tumor progression and cancer stem cell functions

Research Project

Project/Area Number 26430119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionKanagawa Cancer Center Research Institute

Principal Investigator

MIYAZAKI KAORU  地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, その他 (70112068)

Co-Investigator(Renkei-kenkyūsha) MIYAGI Yohei  神奈川県立病院機構, 神奈川県立がんセンター臨床研究所, 総括部長 (00254194)
HIGASHI Shouichi  横浜市立大学, 大学院生命ナノシステム科学研究科, 教授 (10275076)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん微小環境 / 浸潤・転移 / がん幹細胞 / ラミニン / CD44 / 細胞接着 / 細胞外マトリックス / 免疫染色 / がん浸潤 / MMP / 病理診断 / モノクローナル抗体 / ラミニンγ2 / がんマーカー / 浸潤
Outline of Final Research Achievements

The present study investigated functions of the tumor invasion marker laminin gamma2 chain (Lmg2) in tumor progression. 1. The most N-terminal, domain V (dV) of Lmg2 promoted vascular permeability and tumor cell invasion into endothelial cell layer. 2. The dV protein stimulated migration of metastatic breast cancer cells by binding the cancer stem cell marker CD44. However, it was not clear whether dV supports the stem cell function. 3. Novel antibodies recognizing dV were prepared. Analyses with these antibodies revealed that small proteolytic fragments containing dV were highly produced in various cultured human cancer cell lines, cancer tissues and sera of cancer patients. Immunohistochemistry showed that one of dV antibodies detects invasive lung cancer cells at high sensitivity. These results suggest that dV fragments are produced in cancer tissues and contribute to tumor invasion. The dV antibodies seem useful for pathological analysis and diagnosis of human cancers.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2017 2016 2015 2014

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Highly sensitive detection of invasive lung cancer cells by novel antibody against amino-terminal domain of laminin gamma2 chain.2016

    • Author(s)
      Miyazaki, K., Oyanagi, J., Sugino, A., Sato, H., Yokose, T., Nakayama, H., Miyagi, Y.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 12 Pages: 1909-1918

    • DOI

      10.1111/cas.13089

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Amino-terminal fragments of laminin γ2 chain stimulate migration of metastatic breast cancer cells by interacting with CD442015

    • Author(s)
      Sato, H, Oyanagi, J., Komiya, E., Ogawa, T, Higashi, S., Miyazaki, K.
    • Journal Title

      Clin. Exp. Metastasis

      Volume: 32 Issue: 5 Pages: 405-415

    • DOI

      10.1007/s10585-015-9705-6

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Amino-terminal fragments of laminin gamma2 chain retract vascular endothelial cells and increase vascular permeability.2014

    • Author(s)
      Sato, H, Oyanagi, J., Komiya, E., Ogawa, T, Higashi, S., Miyazaki, K.
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 2 Pages: 168-175

    • DOI

      10.1111/cas.12323

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulation of matrix metalloproteinase-9 secretion from tumor-associated macrophage-like cells by proteolytically processed laminin-332 (laminin-5)2014

    • Author(s)
      Kamoshida, G., Ogawa, T., Oyanagi, J., Sato, H., Komiya, E., Higashi, S., Miyazaki, K., Tsuji, T.
    • Journal Title

      Clin. Exp. Metastasis

      Volume: 31 Pages: 285-291

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Angiomodulin (AGM/IGFBP-rP1) is a molecular marker of vascular endothelial cells activated by VEGF in human breast cancers.2014

    • Author(s)
      Komiya, E, Sato, H., Ise, I., Watanabe, N., Higashi, H., Miyagi, Y., Miyazaki, K.
    • Journal Title

      Cancer Med

      Volume: 印刷中 Issue: 3 Pages: 537-549

    • DOI

      10.1002/cam4.216

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of transforming growth factor-β signaling potentiates tumor cell invasion into collagen matrix induced by fibroblast-derived hepatocyte growth factor.2014

    • Author(s)
      Oyanagi, J., Kojima, N., Sato, H., Higashi, S., Kikuchi, K., Sakai, K., Matsumoto, K., Miyazaki, K.
    • Journal Title

      Exp Cell Res.

      Volume: 印刷中 Issue: 2 Pages: 267-279

    • DOI

      10.1016/j.yexcr.2014.04.009

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Tumor invasion marker laminin γ2 chain - highly sensitive detection of invasive lung cancer cells by novel antibody recognizing its N-terminal fragment.2017

    • Author(s)
      Miyazaki, K.
    • Organizer
      BIT’s 10th Annual World Cancer Congress
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2017-05-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Production of N-terminal active fragments of laminin γ2 chain by cultured human cancer cells and in lung cancer tissues.2016

    • Author(s)
      Miyazaki, K., Oyanagi, J., Sato, H., Miyagi, Y.
    • Organizer
      第75回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] N-terminal fragments of laminin γ2 chain stimulate migration of metastatic breast cancer cells by interacting with CD442015

    • Author(s)
      Miyazaki, K., Sato, H., Higashi, S.
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] CD69 induced in CCC cells cultured under serum starvation and hypoxia activates cel surface integrin2015

    • Author(s)
      Kanayama, T., Koizume, S., Miyagi, E., Hirahara, F., Miyazaki, K., Miyagi, Y.
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] がん微小環境における細胞外マトリックス分子の変動と意義2015

    • Author(s)
      宮崎香
    • Organizer
      第33回日本ヒト細胞学会8月22-23日
    • Place of Presentation
      宮崎
    • Year and Date
      2015-08-22 – 2015-08-23
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Three-dimensional collagen gel co-culture model as a tool to investigate tumor invasion: roles of HGF and TGF-beta2014

    • Author(s)
      Miyazaki, K., Jun Oyanagi, J., Shouichi Higashi, S., Kikuchi, K., Sakai, K., Matsumoto, K.
    • Organizer
      日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Laminin gamma2 Chain Interacts with CD44 and Stimulates Migration of Metastatic Breast Cancer Cells2014

    • Author(s)
      Sato, H., Miyazaki, K
    • Organizer
      第23回日本がん転移学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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