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Screening for small molecules modulating epithelial-stromal cell interactions

Research Project

Project/Area Number 18510199
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionMicrobial Chemistry Research Foundation

Principal Investigator

KAWADA Manabu  Microbial Chemistry Research Foundation, Numazu Bio-Medical Research Institute, Drug Development Unit, Leader (20300808)

Co-Investigator(Kenkyū-buntansha) ARAKAWA Masayuki  Microbial Chemistry Research Foundation, Researcher (90398868)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,080,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsAntibiotics / Bioactive substances / Natural products / 生理活性
Research Abstract

1. In vitro coculture system of epithelial and stromal cells of the prostate
Using the in vitro coculture system of human prostate cancer cells and human prostate stromal cells, we screened for compounds that inhibit the stromal cells-accelerated growth of the prostate cancer cells. Among microbial cultured broths of actinomycetes or fungi, we found the activities in several broths.
2. Inhibitors of secretion of an angiogenic factor, angiogenin
We screened for inhibitors of secretion of angiogenin from human prostate cancer cells. As a result, we found the activity in one of fungus cultured broth and purified the active compounds. Structural analyses have revealed that the active compounds are terrein and its novel analogue, terrein glucoside. These compounds were found to inhibit tube formation of endothelial cells suggesting the possibility as anti-angiogenic drugs.
3. Establishment of an in vivo peritoneal dissemination model of gastric cancer
We developed an in vivo peritoneal dissemination model of gastric cancer in order to design a new screening system for modulators of epithelial-stromal cell interactions. We injected the several human gastric cancer cell lines expressing a fluorescent protein, GFP, into nude mice intraperitoneally, and then measured the growth of the intraperioneal cancer cells by imaging GFP. As a result, we found that some of tested gastric cancer cell lines highly formed metastatic foci in the abdomen. We then designed a new coculture system of human gastric stromal cells and the highly metastatic gastric cancer cell line expressing GFP. Using this coculture system we tried to screen for compounds that inhibit the stromal cells-accelerated growth of the gastric cancer cells. We could actually find the activities in some microbial cultured broths.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (40 results)

All 2008 2007 2006

All Journal Article (22 results) (of which Peer Reviewed: 10 results) Presentation (18 results)

  • [Journal Article] Transforming growth factor-β1 modulates tumor-stromal cell interactions of prostate cancer through insulin-like growth factor-I.2008

    • Author(s)
      Kawada,M.,Inoue,H.Aralawa,M., and Ikeda,D.
    • Journal Title

      Anticancer Res. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Transforming growth factor-β1 modulates tumor-stromal cell interactions of prostate cancer through insulin-like growth factor-I.2008

    • Author(s)
      Kawada, M., Inoue, H. Aralawa, M., Ikeda, D.
    • Journal Title

      Anticancer Res. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Highly tumorigenic human androgen receptor-positive prostate cancer cells overexpress angiogenin.2007

    • Author(s)
      Kawada,M.,Inoue,H.,Arakawa,M.,Takamoto,K.,Masuda,T., and Ikeda,D.
    • Journal Title

      Cancer Sci. 98

      Pages: 350-356

    • NAID

      10019481548

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A new proteasome inhibitor, TP-110, induces apoptosis in human prostate cancer PC-3 cells.2007

    • Author(s)
      Momose,I.,Iijima,M.,Kawada,M., and Ikeda,D.
    • Journal Title

      Biosci. Biotechnol. Biochem. 71

      Pages: 1036-1043

    • NAID

      10027513868

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Highly tumorigenic human androgen receptor-positive prostate cancer cells overexpress angiogenin.2007

    • Author(s)
      Kawada, M., Inoue, H., Arakawa, M., Takamoto, K., masuda, T., Ikeda, D.
    • Journal Title

      Cancer Sci 98

      Pages: 350-356

    • NAID

      10019481548

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A new proteasome inhibitor, TP-110, induces apoptosis in human prostate cancer PC-3 cells.2007

    • Author(s)
      Momose, I., Iijima, M., Kawada, M., Ikeda, D.
    • Journal Title

      Biosci. Biotecnol. Biochem. 71

      Pages: 1036-1043

    • NAID

      10027513868

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Highly tumorigenic human androgen receptor-positive prostate cancer cells overexpress angiogenin2007

    • Author(s)
      Kawada, M., Inoue, H., Arakawa, M., Takamoto, K., Masuda, T. Ikeda, D.
    • Journal Title

      Cancer Sci. 98

      Pages: 350-356

    • NAID

      10019481548

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new proteasome inhibitor,TP-110,induces apoptosis in human prostate cancer PC-3 cells2007

    • Author(s)
      Momose, L., Iijima, M., Kawada. M., Ikeda, D.
    • Journal Title

      Biosci.Biotechnol.Biochem 71

      Pages: 1036-1043

    • NAID

      10027513868

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin-like growth factor-I secreted from prostate stromal cells mediates tumor-stromal cell interactions of the prostate cancer.2006

    • Author(s)
      Kawada,M.,Inoue,H.,Masuda,T., and Ikeda,D.
    • Journal Title

      Cancer Res. 66

      Pages: 4419-4425

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Establishment of a highly tumorigenic LNCaP cell line having inflammatory cytokine resistance.2006

    • Author(s)
      Kawada,M.,Inoue,H.,Usami,I.,Takamoto,K.,Masuda,T.,Yamazaki,Y., and Ikeda,D.
    • Journal Title

      Cancer Lett. 242

      Pages: 46-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Inhibitory activity of the hypoxia-induced factor-1 pathway by tartrolone C.2006

    • Author(s)
      Yamazaki,Y.,Someno,T.,Minamiguchi,K.,Kawada,M.,Momose,I.,Kinoshita,N.,Doi,H., and Ikeda,D.
    • Journal Title

      J. Antibiot. 59

      Pages: 693-697

    • NAID

      10019271110

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Antitumor effect of kigamicin D on mouse tumor models.2006

    • Author(s)
      Masuda,T.,Ohba,S.,Kawada,M.,Osono,M.,Ikeda,D.,Esumi,H., and Kunimoto,S.
    • Journal Title

      J. Antibiot. 59

      Pages: 209-214

    • NAID

      10017477695

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Augmentation of cellular immunity by kigamicin D.2006

    • Author(s)
      Masuda,T.,Ohba,S.,Kawada,M.,Iijima,M.Inoue,H.Osono,M.,Ikeda,D., and Kunimoto,S.
    • Journal Title

      J. Antibiot. 59

      Pages: 215-219

    • NAID

      10017477703

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Insulin-like growth factor-I secreted from prostate stromal cells mediates tumor-stromal cell interactions of the prostate cance.2006

    • Author(s)
      Kawada, M., Inoue, H., Masuda, T., Ikeda, D.
    • Journal Title

      Cancer Res. 66

      Pages: 4419-4425

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Establishment of a highly tumorigenic LNCaP cell line having inflammatory cytokine resistance.2006

    • Author(s)
      Kawada, M., Inoue, H., Usami, I., Takamoto, K., Masuda, T., Yamazaki, Y., Ikeda, D.
    • Journal Title

      Cancer Lett. 242

      Pages: 46-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Inhibitory activity of the hypoxia-induced factor-1 pathway by tartrolone C.2006

    • Author(s)
      Yamazaki, Y., Someno, T., Minamiguchi, K., Kawada, M., Momose, I., Kinoshita, N., Doi, H., Ikeda, D.
    • Journal Title

      J. Antibitot. 59

      Pages: 693-697

    • NAID

      10019271110

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Antitumor effect of kigamicin D on mouse tumor models.2006

    • Author(s)
      Masuda, T., Ohba, S., Kawada, M., Osono, M., Ikeda, D., Esumi, H., Kunimoto, S.
    • Journal Title

      J. Antibiot. 59

      Pages: 209-214

    • NAID

      10017477695

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
  • [Journal Article] Augmentation of cellular immunity by kigamicin D.2006

    • Author(s)
      Masuda, T., Ohba, S., Kawada, M., Iijima, M. Inoue, H. Osono, M., Ikeda, D., Kunimoto, S.
    • Journal Title

      J. Antibiot. 59

      Pages: 215-219

    • NAID

      10017477703

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Inhibitory activity of the hypoxia-induced factor-1 pathway by tartrolone C.2006

    • Author(s)
      Yamazaki, Y., Someno, T., Minamiguchi, K., Kawada, M., Momose, I., Kinoshita, N., Doi, H., Ikeda, D.
    • Journal Title

      J. Antibiot. 59

      Pages: 693-697

    • NAID

      10019271110

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Augmentation of cellular immunity by kigamicin D.2006

    • Author(s)
      Masuda, T., Ohba, S., Kawada, M., Iijima, M., Inoue, H., Osono, M., Ikeda, D., Kunimoto, S.
    • Journal Title

      J. Antibiot. 59

      Pages: 215-219

    • NAID

      10017477703

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Insulin-like growth factor-I secreted from prostate stromal cells mediates tumor-stromal cell interactions of the prostate cancer.2006

    • Author(s)
      Kawada, M., Inoue, H., Masuda, T., Ikeda, D.
    • Journal Title

      Cancer Res. 66

      Pages: 4419-4415

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Establishment of a highly tumorigenic LNCaP cell line having inflammatory cytokine resistance.2006

    • Author(s)
      Kawada, M., Inoue, H., Usami, I., Takamoto, K., Masuda, T., Yamazaki, Y, Ikeda, D.
    • Journal Title

      Cancer Lett. 242

      Pages: 46-52

    • Related Report
      2006 Annual Research Report
  • [Presentation] Transforming growth factor-β1 modulates tumor-stromal cell interactions of prostate cancer through insulin-like growth factor-I.2007

    • Author(s)
      M.Kawada,M.Arakawa,H.Inoue,I.Momose, and D.Ikeda
    • Organizer
      19th AACR-NCI-EORTC International Conference "Molecular Targets and Cancer Therapeutics"
    • Place of Presentation
      サンフランシスコ(米国)
    • Year and Date
      2007-10-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Transforming growth factor-b1 modulates tumor-stromal cell interactions of prostate cancer through insulin-like growth factor-I.2007

    • Author(s)
      Kawada, M., Arakawa, M., Inoue, H., Momose, I., Ikeda, D.
    • Organizer
      19th AACR-NCI-EORTC International Conference Molecular Targets and Cancer Therapeutics
    • Place of Presentation
      San Francisco(USA)
    • Year and Date
      2007-10-24
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Transforming growth factor-β1 modulates tumor-stromal cell interactions of prostate cancer through insulin-like growth factor-I2007

    • Author(s)
      M. Kawada, M. Arakawa, H. Inoue, I. Momose, and D. Ikeda
    • Organizer
      19th AACR-NCI-EORTC International Conference"Molecular Targets and Cancer Therapeutics"
    • Place of Presentation
      サンフランシスコ(米国)
    • Year and Date
      2007-10-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] Suppression of prostate cancer by leucinostatins through the tumor-stromal cell interactions.2007

    • Author(s)
      M.Kawada,M.Arakawa,T.Masuda, and D.Ikeda
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Suppression of prostate cancer by leucinostatins through the tumor-stromal cell inetractions.2007

    • Author(s)
      Kawada, M., Arakawa, M., Masuda, T., Ikeda, D.
    • Organizer
      66th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Suppression of prostate cancer by leucinostatins through the tumor-stromal cell interactions2007

    • Author(s)
      M. Kawada, M. Arakawa, T. Masuda, D. Ikeda
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] TGF-βによる前立腺癌-間質相互作用の変化2007

    • Author(s)
      川田 学
    • Organizer
      第16回日本がん転移学会総会
    • Place of Presentation
      富山
    • Year and Date
      2007-07-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] TGF-βmodulates the tumor-stromal cell interactions of prostate cancer.2007

    • Author(s)
      Kawada, M.
    • Organizer
      16ty Annual Meeting of Japanese Association for Metastasis Research
    • Place of Presentation
      Toyama
    • Year and Date
      2007-07-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] TGF-βによる前立腺間質IGFaxisの調節2007

    • Author(s)
      川田 学、荒川正行、増田 徹、池田大四郎
    • Organizer
      第11回がん分子標的治療研究会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-07-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] TGF-βmodulates the IGF axis in prostate stromal cells.2007

    • Author(s)
      Kawada, M., Arakawa, M., Masuda, T., Ikeda, D.
    • Organizer
      11th Annual Meeting of the Japanese Association for Molecular Target Therapy of Cancer
    • Place of Presentation
      Osaka
    • Year and Date
      2007-07-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Insulin-like growth factor-I secreted from prostate stromal cells mediates tumor-stromal cell interactions of prostate cancer.2006

    • Author(s)
      M.Kawada,H.Inoue,T.Masuda, and D.Ikeda
    • Organizer
      18th EORTC-NCI-AACR symposium on "Molecular Targets and Cancer Therapeutics"
    • Place of Presentation
      プラハ(チェコ)
    • Year and Date
      2006-11-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Insulin-lkie growth factor-I secreted from prostate stromal cells mediates tumor-stromal cell interactions of prostate cancer.2006

    • Author(s)
      Kawada, M., Inoue, H., Masuda, T., Ikeda, D.
    • Organizer
      18th EORTC-NCI-AACR symposium on Molecular Targets and Cancer Therapeutics
    • Place of Presentation
      Prague(Chez)
    • Year and Date
      2006-11-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 前立腺癌-間質相互作用に及ぼすTGF-βシグナルの解析2006

    • Author(s)
      川田 学、荒川正行、増田 徹、池田大四郎
    • Organizer
      第65回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effect of TGF-βon the tumor-stromal cell interactions of prostate cancer.2006

    • Author(s)
      Kawada, M., Arakawa, M., Masuda, T., Ikeda, D.
    • Organizer
      65th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Insulin-like growth factor-I secreted from prostate stromal cells mediates tumor-stromal cell interactions of the prostate cancer.2006

    • Author(s)
      M.Kawada,H.Inoue,T.Masuda, and D.Ikeda
    • Organizer
      第11回国際がん転移学会・第15回日本がん転移学会合同会議
    • Place of Presentation
      徳島
    • Year and Date
      2006-09-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Insulin-like growth factor-I secreted from prostate stromal cells mediates tumor-stromal cell interactions of the prostate cancer.2006

    • Author(s)
      Kawada, M., Inoue, H., Masuda, T., Ikeda, D.
    • Organizer
      The 11th International congress of metastasis Research Society Jointed with the 15th Annual Meeting of Japanese Association for Metastasis Research
    • Place of Presentation
      Tokushima
    • Year and Date
      2006-09-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 前立腺間質細胞が産生するIGF-Iによる前立腺癌細胞の増殖2006

    • Author(s)
      川田 学、増田 徹、池田大四郎
    • Organizer
      第10回がん分子標的治療研究会総会
    • Place of Presentation
      東京
    • Year and Date
      2006-06-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] IGF-I secreted from prostate stromal cells stimulates the prostate cancer.2006

    • Author(s)
      Kawada, M., Masuda, T., Ikeda, D.
    • Organizer
      10th Annual Meeting of the Japanese Association for Molecular Target Therapy of Cancer
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-06-15
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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