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Analysis of factors associated with the development of gastric cancer in hypoxic microenvironment

Research Project

Project/Area Number 23390329
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionOsaka City University

Principal Investigator

YASHIRO Masakazu  大阪市立大学, 医学(系)研究科(研究院), 准教授 (60305638)

Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords癌周囲低酸素環境 / 胃癌 / スキルス胃癌細胞 / 癌関連線維芽細胞 / CXCL12 / CXCR4 / 分子標的治療 / スキルス胃癌 / 癌幹細胞 / 癌由来線維芽細胞 / 低酸素 / 胃癌細胞 / 線維芽細胞 / 癌微小環境 / 筋線維芽細胞 / CA-9
Outline of Final Research Achievements

This study investigated the growth-signaling of gastric cancer (GC) cells in focus on the interaction with cancer-associated fibroblasts (CAFs) and gastric cancer (GC) cells under normoxia and hypoxia. Nine cell lines, including four diffuse-type GC cell lines, two intestinal-type GC cell lines, and three CAF cell lines were used. Cells were examined for expression CXCR4, FGFR2 and SDF1. CXCR4 expression by diffuse-type GC cells was significantly increased in hypoxia, while FGFR2 expression was decreased. FGFR2 inhibition significantly decreased the activity of CAFs for diffuse-type GC cells in normoxia but not in hypoxia. In contrast, CXCR4 inhibition significantly decreased the activity of CAFs in hypoxia. HIF1 siRNA significantly decreased both CXCR4 expression by diffuse-type GC cells and SDF1 production by CAFs. These findings suggest that diffuse-type GC cells might switch their driver pathways from FGFR2 signaling to SDF1/CXCR4 axis through HIF1 in hypoxic microenvironments.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (36 results)

All 2015 2014 2013 2012 Other

All Journal Article (20 results) (of which Peer Reviewed: 18 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (11 results) (of which Invited: 2 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts.2015

    • Author(s)
      Satoyoshi R, Kuriyama S, Aiba N, Yashiro M, Tanaka M.
    • Journal Title

      Oncogene.

      Volume: 34 Issue: 5 Pages: 650-660

    • DOI

      10.1038/onc.2013.584

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection2014

    • Author(s)
      Kiga K et.al
    • Journal Title

      Nat Commun

      Volume: 5 Issue: 1 Pages: 4497-4497

    • DOI

      10.1038/ncomms5497

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-beta signaling.2014

    • Author(s)
      Hasegawa T, Yashiro M, Nishii T, Matsuoka J, Fuyuhiro Y, Morisaki T, Fukuoka T, Shimizu K, Shimizu T, Miwa A, Hirakawa K.
    • Journal Title

      Int J Cancer

      Volume: 134 Issue: 8 Pages: 1785-95

    • DOI

      10.1002/ijc.28520

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lysyl oxidase-like 2 (LOXL2) from stromal fibroblasts stimulates the progression of gastric cancer.2014

    • Author(s)
      Kasashima H, Yashiro M, Kinoshita H, Fukuoka T, Morisaki T, Masuda G, Sakurai K, Kubo N, Ohira M, Hirakawa K
    • Journal Title

      Cancer Lett.

      Volume: 354 Issue: 2 Pages: 438-446

    • DOI

      10.1016/j.canlet.2014.08.014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer2014

    • Author(s)
      Yutaka Naito, Kyohei Yasuno, Hiroko Tagawa, Naoya Sakamoto, Naohide Oue, Masakazu Yashiro, Kazuhiro Sentani, Keisuke Goto, Shunsuke Shinmei, Htoo Zarni Oo, Kazuyoshi Yanagihara, Kosei Hirakawa, Wataru Yasui
    • Journal Title

      Oncology Reports

      Volume: 32 Issue: 4 Pages: 1720-1726

    • DOI

      10.3892/or.2014.3333

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Comparative proteomics analysis of gastric cancer stem cells2014

    • Author(s)
      Morisaki T, Yashiro M, Kakehashi A, Inagaki A, Kinoshita H, Fukuoka T, Kasashima H, Masuda G, Sakurai K, Kubo N, Muguruma K, Ohira M, Wanibuchi H, Hirakawa K.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 11 Pages: e110736-e110736

    • DOI

      10.1371/journal.pone.0110736

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The niche component periostin is produced by cancer-associated fibroblasts, supporting growth of gastric cancer through ERK activation2014

    • Author(s)
      Kikuchi Y, Kunita A, Iwata C, Komura D, Nishiyama T, Shimazu K, Takeshita K, Shibahara J, Kii I, Morishita Y, Yashiro M, Hirakawa K, Miyazono K, Kudo A, Fukayama M, Kashima TG.
    • Journal Title

      Am J Pathol.

      Volume: 184 Issue: 3 Pages: 859

    • DOI

      10.1016/j.ajpath.2013.11.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Stromal fibroblasts mediate extracellular matrix remodeling and invasion of scirrhous gastric carcinoma cells.2014

    • Author(s)
      Yamaguchi H, Yoshida H, Takanashi M, Ito Y, Fukami K, Yanagihara K, Yashiro M, Sakai R.
    • Journal Title

      PlosOne

      Volume: 9 Issue: 1 Pages: e85485-e85485

    • DOI

      10.1371/journal.pone.0085485

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A c-Met inhibitor increases the chemosensitivity of cancer stem cells to the irinotecan in gastric carcinoma.2013

    • Author(s)
      Yashiro M, Nishii T, Hasegawa T, Matsuzaki T, Morisaki T, Fukuoka T, Hirakawa K.
    • Journal Title

      Br J Cancer

      Volume: 109 Issue: 10 Pages: 2619-28

    • DOI

      10.1038/bjc.2013.638

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heregulin Induces Resistance to Lapatinib-mediated Growth Inhibition of HER2-Amplified Cancer Cells.2013

    • Author(s)
      Sato Y
    • Journal Title

      Cancer Sci

      Volume: 104 Issue: 12 Pages: 1618-1625

    • DOI

      10.1111/cas.12290

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design and synthesis of a series of a-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved a queous solubility.2013

    • Author(s)
      Masao Ohashi, et.al.
    • Journal Title

      Bioorg. Med Chem.

      Volume: 21 Issue: 8 Pages: 2319-2332

    • DOI

      10.1016/j.bmc.2013.02.003

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia Stimulates the EMT of Gastric Cancer Cells through Autocrine TGFb Signaling.2013

    • Author(s)
      Matsuoka J, Yashiro M, Doi Y
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 5 Pages: e62310-e62310

    • DOI

      10.1371/journal.pone.0062310

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cancer-associated orthotopic myofibroblasts stimulates the motility of gastric carcinoma cells2012

    • Author(s)
      (Fuyuhiro Y), Yashiro M,, Noda S, Matsuoka J, Hasegawa T, Kato Y, Sawada T, Hirakawa K.
    • Journal Title

      Cancer Science

      Volume: 103 Issue: 4 Pages: 797-805

    • DOI

      10.1111/j.1349-7006.2012.02209.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PI3K/Akt signalling is required for the attachment and spreading, and growth in vivo of metastatic scirrhous gastric carcinoma2012

    • Author(s)
      (Matsuoka T), Yashiro M,, Nishioka N, Hirakawa K, Olden K, Roberts JD
    • Journal Title

      British journal of cancer

      Volume: 106 Issue: 9 Pages: 1535-42

    • DOI

      10.1038/bjc.2012.107

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumourigenic capacity of diffuse-type gastric carcinoma-initiating cells is inhibited by TGF-β2012

    • Author(s)
      Katsuno Y
    • Journal Title

      J Pathol

      Volume: 228 Issue: 3 Pages: 391-404

    • DOI

      10.1002/path.4020

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of the stemness factors sox2, oct3/4, and nanog in gastric carcinoma2012

    • Author(s)
      Matsuoka J, Yashiro M,, Sakurai K, Kubo N, Tanaka H, Muguruma K, Sawada T, Ohira M, Hirakawa K.
    • Journal Title

      J Surg Res.

      Volume: 174 Issue: 1 Pages: 130-135

    • DOI

      10.1016/j.jss.2010.11.903

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] スキルス胃癌の増殖進展機序2012

    • Author(s)
      (八代正和)、大平雅一、六車一哉、神籐理、平川弘聖
    • Journal Title

      日本臨牀

      Volume: 70 Pages: 1812-1815

    • Related Report
      2012 Annual Research Report
  • [Journal Article] スキルス胃癌の浸潤・転移-腹膜播種形成の分子機構-2012

    • Author(s)
      (八代正和),冬廣雄彦、松岡順子、長谷川毅、野田諭,平川弘聖
    • Journal Title

      臨牀消化器内科

      Volume: 27 Pages: 1185-89

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Plasminogen activator inhibitor 1 RNAi suppresses gastric cancer metastasis in vivo2012

    • Author(s)
      Nishioka N, Matsuoka T, Yashiro M,, Hirakawa K, Olden K, Roberts JD
    • Journal Title

      Cancer Science

      Volume: 103 Issue: 2 Pages: 228-32

    • DOI

      10.1111/j.1349-7006.2011.02155.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NC-6301, a polymeric micelle rationally optimized for effective release of docetaxel, is potent but is less toxic than native docetaxel in vivo2012

    • Author(s)
      Harada M, Iwata C, Saito H, Ishii K, Hayashi T, Yashiro M,, Hirakawa K, Miyazono K, Kato Y, Kano MR
    • Journal Title

      Int J Nanomedicine

      Volume: 7 Pages: 2713-27

    • DOI

      10.2147/ijn.s31247

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Bone marrow derived mesenchymal stem cells are associated with the tumor microenvironment of gastric tumor2014

    • Author(s)
      Kasashima H, Yashiro M, Masuda G, Morisaki T, Fukuoka T, Hasegawa T, Hirakawa K
    • Organizer
      International Society for Stem Cell Research (ISSCR) 12th Annual Meeting
    • Place of Presentation
      Vancouver (Canada)
    • Year and Date
      2014-06-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] The stemness of gastric cancer stem cells is sustained by TGFβ produced from cancer-associated fibroblasts2014

    • Author(s)
      Yashiro M, Hasegawa T, Fukuoka T, Kinoshita H, Morisaki T, Kasashima H, Masuda G, Kubo N, Hirakawa K
    • Organizer
      American Association for Cancer Research 105th Annual Meeting 2014
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2014-04-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effect of cancer associated fibroblast on gastric cancer cells under hypoxia2014

    • Author(s)
      Kinoshita H, Yashiro M, Masuda G, Kasashima H, Morisaki T, Fukuoka T, Shibutani M, Yamazoe S, Sakurai K, Nagahara H, Kimura K, Toyokawa T, Amano R, Kubo N, Tanaka H, Muguruma K, Ohtani H, Maeda K, Ohira M, Hirakawa K
    • Organizer
      American Association for Cancer Research 105th Annual Meeting 2014
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2014-04-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] The effect of PGE2 receptor inhibitor on the microenviroment of scirrhous gastric cancer2014

    • Author(s)
      Fukuoka T, Yashiro M, Takeda H, Maruyama T, Kasashima H, Masuda G, Kinoshita H, Morisaki T, Sakurai K, Shibutani M, Yamazoe S, Kimura K, Nagahara H, Toyokawa T, Amano R, Kubo N, Tanaka H, Muguruma K, Ohtani H, Maeda K, Ohira M, Hirakawa K
    • Organizer
      American Association for Cancer Research 105th Annual Meeting 2014
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2014-04-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of lysyl oxidase and lysyl oxidase-like 2 in gastric carcinoma2014

    • Author(s)
      Kasashima H, Yashiro M, Go Y, Masuda G, Kinoshita H, Tokumoto M, Morisaki T, Fukuoka T, Toyokawa T, Kubo N, Tanaka H, Muguruma K, Ohira M, Hirakawa K
    • Organizer
      American Association for Cancer Research 105th Annual Meeting 2014
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2014-04-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] A c-Met inhibitor increases the chemosensitivity of cancer stem cells to the irinotecan active metabolite SN38 in gastric carcinoma2013

    • Author(s)
      Yashiro M
    • Organizer
      American Association for Cancer Research 104rd Annual Meeting 2013.
    • Place of Presentation
      Washington DC Convention Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular mechanisms responsible for scirrhous gastric cancer and novel targeting therapies.2013

    • Author(s)
      Yashiro M
    • Organizer
      The 4th JCA-AACR Special Joint Conference.
    • Place of Presentation
      Chiba Tokyo Bay Maihama Hotel Club & Resorts
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] スキルス胃癌の増殖進展における癌周囲微小環境と癌細胞との相互作用2013

    • Author(s)
      八代正和
    • Organizer
      第10回日本病理学会カンファレンス
    • Place of Presentation
      神戸 六甲ホテル
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Cancer-associated Fibroblasts Might Sustain the Stemness of Scirrhous Gastric Cancer Cells by TGFb Signalings2013

    • Author(s)
      Yashiro M
    • Organizer
      AACR/JCA Joint Conference: Breakthroughs in Basic and Translational Cancer Research
    • Place of Presentation
      Hyatt Regency Maui, Maui, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] スキルス胃癌の増殖進展機序と分子標的治療2013

    • Author(s)
      八代正和
    • Organizer
      第85回日本胃癌学会
    • Place of Presentation
      大阪国際会議場、大阪
    • Related Report
      2012 Annual Research Report
  • [Presentation] An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells2012

    • Author(s)
      Yashiro M
    • Organizer
      American Association for Cancer Research 103rd Annual Meeting
    • Place of Presentation
      Convention Center, Chicago, USA
    • Related Report
      2012 Annual Research Report
  • [Book] 最新胃癌学2014

    • Author(s)
      八代正和
    • Total Pages
      751
    • Publisher
      日本臨牀
    • Related Report
      2013 Annual Research Report
  • [Remarks] 大阪市立大学大学院 医学研究科 腫瘍外科学 腫瘍病態学講座

    • URL

      http://www.med.osaka-cu.ac.jp/surgical-oncology/relation/geriatric_oncology.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 老年腫瘍病態学講座

    • URL

      http://www.med.osaka-cu.ac.jp/surgical-oncology/relation/geriatric_oncology.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 老年腫瘍病態学講座

    • URL

      http://www.med.osaka-cu.ac.jp/surgical-oncology/relation/geriatric_oncology.html

    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] プロスタグランジンD2合成酵素を利用した消化器癌治療剤2013

    • Inventor(s)
      2013/12/26
    • Industrial Property Rights Holder
      2013/12/26
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-268465
    • Filing Date
      2013-12-26
    • Related Report
      2013 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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