• Search Research Projects
  • Search Researchers
  1. Back to previous page

Molecular analysis of compensatory mechanism which tumor cells exert in VEGF deficent/RipTag mouse

Research Project

Project/Area Number15590363
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionOsaka Medical Center for Cancer and Cardiovascular Diseases

Principal Investigator

INOUE Masahiro  OMCC, Biochemistry, director, 主任研究員 (10342990)

Co-Investigator(Kenkyū-buntansha) MUKAI Mutsuko  MUKAI,Mutsuko, 主任研究員 (20342991)
Project Period (FY) 2003 – 2004
Project Status Completed(Fiscal Year 2004)
Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 2004 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 2003 : ¥1,900,000 (Direct Cost : ¥1,900,000)
Keywordsangiogenesis / VEGF / transgenic mouse / gene knockout mouse / hypoxia / 遺伝子発現
Research Abstract

While we transferred RipTag mice from university of California at San Francisco, we found profound reduction of tumor formation in Japan. Formation of tumor in RipTag mouse is known to be sensitive to the genetic background. Although we tried to resolve the problem by backcrossing it into C57B1/6N or DBA background, we did not observe remarkable recovery of tumor formation. Afterwards, it has been revealed that the same phenomenon was observed in the original mouse colony in UCSF. It is likely that some genomic change in RipTag mouse occurred. Re-establishment of the transgenic mouse is now under consideration. Meanwhile, analysis of the archive pancreas samples from RipTag/VEGF-/- mice revealed that there were residual tumors with quite low microvessel density without apparent necrosis. We found that the residual tumors contains broad hypoxic region. This finding suggests that inhibiting angiogenesis results in emergence of hypoxic region as well as reduction of tumor formation. In these hypoxic tumors, apoptosis was not significantly increased, tumor cells seems to survive by adapting to the hypoxic microenvironment. From clinical point of view, the results offered a serious issue that anti-angiogenesis therapy might induce drug resistance by selecting hypoxia tolerant cancer cells. Then, We started to investigate the molecular mechanism of hypoxia tolerance of malignant cells. We found various cell lines can be maintained in hypoxic conditions for a couple of weeks. These tumor cells were alive but no proliferation nor cell death was observed. We focused on the mTOR signaling, which is know to be suppressed in hypoxia, but the consequence has not been clarified yet. We revealed that suppression of mTOR signaling is critical for their survival under prolonged hypoxic conditions.

Report

(3results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report

Research Products

(25results)

All 2005 2004 2003 Other

All Journal Article Publications

  • [Journal Article] Suppression of PI3K/mTOR pathway rescues LLC cells from cell death induced by hypoxia2005

    • Author(s)
      Hamanaka, Y., Mukai, M., Inoue, M.
    • Journal Title

      Biochem Biophys Res Commun 380

      Pages : 318-326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Transforming growth factor-betal induces LM07 while enhancing the invasiveness of rat ascites hepatoma cells2005

    • Author(s)
      Nakamura, H., Mukai, M., Inoue, M.
    • Journal Title

      Cancer Lett 220

      Pages : 95-99

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis2004

    • Author(s)
      Giraudo, E., Inoue, M., hanahan
    • Journal Title

      J Clin Invest 114

      Pages : 623-633

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Targeting hypoxic cancer cells with a protein prodrug is effective in experimental malignant ascites2004

    • Author(s)
      Inoue, M., Mukai, M., Hamanaka, Y.
    • Journal Title

      Int J Oncol 25

      Pages : 713-720

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] CD4+ T cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer2004

    • Author(s)
      Daniel, D., Chiu, C, Inoue, M.
    • Journal Title

      Cancer Res 65

      Pages : 2018-2025

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis2004

    • Author(s)
      Giraudo, E., Inoue, M., Hanahan, D.
    • Journal Title

      J Clin Invest 114

      Pages : 623-633

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CD4+ T cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer2004

    • Author(s)
      Daniel, D., Chiu, C., Inoue, M.
    • Journal Title

      Cancer Res 65

      Pages : 2018-2025

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis2004

    • Author(s)
      Giraudo, E., Inoue, M., Hanahan, D
    • Journal Title

      J Clin Invest 114

      Pages : 623-633

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CD4+ T cell-mediated antigen-specific immunotherapy in a mouse_model of cervical cancer2004

    • Author(s)
      Daniel, D., Chiu, C.Inoue, M.
    • Journal Title

      Cancer Res 65

      Pages : 2018-2025

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transforming growth factor-beta1 induces LMO7 while enhancing the invasiveness of rat ascites hepatoma cells2004

    • Author(s)
      Nakamura, H., Mukai, M., Inoue, M.
    • Journal Title

      Cancer Lett 220

      Pages : 95-99

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma.2003

    • Author(s)
      Hoffman, J., Giraudo, E., Singh, M., Inoue, M et al.
    • Journal Title

      Cancer Cell 4

      Pages : 383-391

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tumor Hypoxia : a Target for Selective Cancer Therapy2003

    • Author(s)
      Kizaka-Kondoh, S., Inoue, M., Harada, H., Hiraoka, M
    • Journal Title

      Cancer Science 94

      Pages : 1021-1028

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of lysophosphatidic acid-induced RhoA activation and tumor cell invasion by 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors2003

    • Author(s)
      Kusama, T., Mukai, M., Inoue, M et al.
    • Journal Title

      Int J Oncol 23

      Pages : 1173-1178

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Selective inhibition of cancer cell invasion by a geranylgeranyltransferase-I inhibitor2003

    • Author(s)
      Kusama, T., Mukai, M., Inoue, M et al.
    • Journal Title

      Clin Exp Metastasis 20

      Pages : 561-567

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclic phosphatidic acid inhibits RhoA-mediated autophosphorylation of FAK at Tyr-397 and subsequent tumor-cell invasion2003

    • Author(s)
      Mukai, M., Iwasaki, Inoue M et al.
    • Journal Title

      Int J Oncol 22

      Pages : 1247-1256

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma.2003

    • Author(s)
      Hoffman, J., Giraudo, E., Singh, M., Inoue, M.et al.
    • Journal Title

      Cancer Cell 4

      Pages : 383-391

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tumor Hypoxia: a Target for Selective Cancer Therapy2003

    • Author(s)
      Kizaka-Kondoh, S., Inoue, M., Harada, H., Hiraoka, M.
    • Journal Title

      Cancer Science 94

      Pages : 1021-1028

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of lysophosphatidic acid-induced RhoA activation and tumor cell invasion by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors2003

    • Author(s)
      Kusama, T., Mukai, M., Inoue, M.et al.
    • Journal Title

      Int J Oncol 23

      Pages : 1173-1178

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Selective inhibition of cancer cell invasion by a geranylgeranyltransferase-I inhibitor2003

    • Author(s)
      Kusama, T., Mukai, M., Inoue, M.et al.
    • Journal Title

      Clin Exp Metastasis 20

      Pages : 561-567

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclic phosphatidic acid inhibits RhoA-mediated autophosphorylation of FAK at Tyr-397 and subsequent tumor-cell invasion2003

    • Author(s)
      Mukai, M., Iwasaki, Inoue, M.et al.
    • Journal Title

      Int J Oncol 22

      Pages : 1247-1256

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Hoffman, J., Giraudo, E., Singh, M., Inoue, M et al.: "Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma."Cancer Cell. 4. 383-391 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kizaka-Kondoh, S., Inoue, M., Harada, H., Hiraoka, M: "Tumor Hypoxia : a Target for Selective Cancer Therapy"Cancer Science. 94. 1021-1028 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kusama, T., Mukai, M., Inoue, M et al.: "Inhibition of lysophosphatidic acid-induced RhoA activation and tumor cell invasion by 3-hydroxy-3-methylglutaryl- coenzyme A reductase inhibitors"Int J Oncol. 23. 1173-1178 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kusama, T., Mukai, M., Inoue, M et al.: "Selective inhibition of cancer cell invasion by a geranylgeranyltrans ferase-I inhibitor"Clin Exp Metastasis. 20. 561-567 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mukai, M., Iwasaki, Inoue, M et al.: "Cyclic phosphatidic acid inhibits RhoA-mediated autophosphorylation of FAK at Tyr-397 and subsequent tumor-cell invasion"Int J Oncol. 22. 1247-1256 (2003)

    • Related Report
      2003 Annual Research Report

URL :

Published : 2003-04-01   Modified : 2016-04-21  

Information FAQ News Terms of Use

Powered by NII kakenhi