Screening for small molecules modulating epithelial-stromal cell interactions

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18510199
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Microbial 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
• Keywords: Antibiotics / Bioactive substances / Natural products

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.

Research Products

• [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
  • 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
• [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
  • Description: 「研究成果報告書概要(和文)」より
  • 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
  • Description: 「研究成果報告書概要(和文)」より
  • 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
  • Description: 「研究成果報告書概要(欧文)」より
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [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
  • 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
  • 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
  • Description: 「研究成果報告書概要(和文)」より
  • 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
  • Description: 「研究成果報告書概要(和文)」より
  • 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
  • Description: 「研究成果報告書概要(和文)」より
  • 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
• [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
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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