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INHIBITION OF LUNG CANCER INVASION AND METASTASIS BY NOVEL ANGIOGENESIS INHIBITORS

Research Project

Project/Area Number 13670616
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionJUNTENDO UNIVERSITY

Principal Investigator

TAKAHASHI Kazuhisa  JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROF., 医学部, 助教授 (80245711)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Fumiyuki  JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, INSTRUCTOR, 医学部, 助手 (70327823)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsOSTEOPONTIN / ENDOSTATIN / LUNG CANCER / ANGIOGENESIS / VEGF / 浸潤 / 転移
Research Abstract

Endostatin (ES), a carboxyl-terminal fragment of type XVIII collagen, which shows a strong anti-angiogenic activity, has been introduced to several clinical studies. Opposite to the initial expectation, the efficacy of ES is inconsistent, suggesting more detail investigations using animal model are required. The purpose of this study is to determine the effect of ES gene transfer on in vivo tumor growth in a murine model. A ung cancer cell line, Lewis Lung Carcinoma (LLC), was transfected with ES gene to, express and secrete ES by lipofectin. After clones were selected to secrete ES by ELISA, several stable transfectants with ES gene (LLC/ES) and control transfectants (LLC/mock) were established. In vitro proliferation using MTT assay of these transfectants demonstrated similar growing speed. In contrast to previous reports, in vivo subcutaneous tumorignecity of LLC/ES transfectants are significantly greater than that of LLC/mock transfectants. Immunohistochemical staining analysis using anti-CD31 antibody demonstrated that ES gene transfer induced angiogenesis, suggesting coinduction of another gene implicated in neovascularization. As expected, LLC/ES transfectants secreted not only ES but also vascular endothelial growth factor (VEGF) to much greater than LLC/mock transfectants. Interestingly, culture supernatants of LLC/ES cells enhanced in vitro proliferation of human umbilical vein endothelial cells (HUVEC) to much greater than those of LLC/mock cells. These results indicate that ES gene transfer in murine lung carcinoma cells induces VEGE secretion, resulting in enhanced in vivo tumorigenecity in a murine model. More attention should be paid for ES gene therapy into lung cancer cells because it may affect other genes expression, which upregulates angiogenesis.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Takahashi F: "Osteopontin induces angiogenesis of murine neuroblastoma cells in mice"Int.J.Cancer. 98. 707-712 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi K: "Restoration of CD44S in non-small cell lung cancer cells enhanced their susceptibility to the macrophage cytotoxicity"Lung cancer. 41. 145-153 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirama M: "Osteopontin overproduced by tumor cells as a potent angiogenic factor contributing to tumor growth"Cancer letters. 198. 107-117 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi F: "Osteopontin is strongly expressed by activated alveolar macrophages in the lungs of acute respiratory distress syndrome"Lung. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi F, Akutagawa S, Fukumoto H, Tsukiyama S, Ohe Y, Takahashi K, Fukuchi Y, Saijo N, Nishio K.: "Osteopontin induces angiogenesis of murine neuroblastoma cells in mice"Int.J.Cancer. 98. 707-712 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi K, Takahashi F, Hirama M, Tanabe KK,. Fukuchi Y.: "Restoration of CD44S in non-small cell lung cancer cells enhanced their susceptibility to the macrophage cytotoxicity"Lung Cancer. 41. 145-153 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirama M, Takahashi F, Takahashi K, Akutagawa S, Shimizu K, Fukuchi Y.: "Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth"Cancer letters. 198. 107-117 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi F, Takahashi F, Shimizu K, Ri C, Tada N, Takahashi H, Soma S, Fukuchi Y.: "Osteopontin is strongly expressed by activated alveolar macrophages in the lungs of acute respiratory distress syndrome"Lung. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi K: "Restoration of CD44S in non-small cell lung cancer cells enhanced their susceptibility to the macrophage cytotoxicity"Lung. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirama M: "Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth"Cancer lett. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhang J. et al.: "Differential osteopontin expression in lung cancer"Cancer Letter. 171. 215-222 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi F. et al.: "Osteopontin induces Angiogenesis of Murine Neuroblastoma cells in Mice"Int J Cancer. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maeda K. et al.: "Distinct Roles of Osteopontin Fragments in the Development of the Pulmonary Involvement in Sarcoidosis"Lung. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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