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Suppression of tumor growth and metastasis via apoptosis induced specifically in endothelial cells by caspin/PEDF/EPC-1

Research Project

Project/Area Number 11670228
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionAichi Medical University School of Medicine

Principal Investigator

SAGA Shinsuke  Aichi Medical University, School of Medicine, Professor, 医学部, 教授 (40144141)

Co-Investigator(Kenkyū-buntansha) ISHIGURO Naoki  Nagoya University, School of Medicine, Lecturer, 大学院・医学部, 講師 (20212871)
KAZAKI Ken-ichi  Aichi Medical University, School of Medicine, Lecturer, 医学部, 助手 (50270715)
YOSHIKAWA Kazuhiro  Aichi Medical University, School of Medicine, Lecturer, 医学部, 講師 (60109759)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordscaspin / PEDF / EPC-1 / apaptosis / endothelial cell / angiogenesis / tumor growth / tumor metastasis / collagen / 血管新生 / deletion mutants / 抗ヒトcaspin抗体
Research Abstract

We investigated the physiological and pathophysiological roles of caspin/PEDF/EPC-1 in tumor growth and metastasis as an inhibitor of angiogenesis. Overexpression of caspin in murine and human cancer cell lines with a high capability of lung metastasis did not affect the cell growth in vitro, but did significantly suppress both tumor growth in vivo and lung metastasis. The density of microvessels was significantly reduced in tumors formed by s.c. inoculation of cancer cells when caspin was overexpressed, indicating that caspin can cause the inhibition of tumor angiogenesis. In addition, supplement of recombinant caspin in the cultures evidently inhibited ex vivo outgrowth of microvessels from excised rat aorta and in vitro growth of cultured endothelial cells in a dose-dependent manner. Furthermore, we found that caspin can induce apoptosis specifically in endothelial cells, but not in any other type of cultured cells. These findings suggest that caspin/PEDF/EPC-1 regulates angiogenesis by inducing apoptosis of endothelial cells. Thus, this protein might play a crucial role in important biological events, in which tissue reconstruction with prominent angiogenesis is essentially required, such as embryogenesis, wound healing, and the formation of granulation tissue as well as tumor growth and metastasis.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Kozaki,K., et al.: "Establishment and characterization of a human cancer cell line NCI-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation."Cancer Res.. 69. 2535-2540 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hida,T., et al.: "Cyclooxygenase (COX)-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines."Clin.Cancer Res.. 6. 2006-2011 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hamajima, N., et al.: "Polymerase Chain Reaction with Confronting Two-pair Primers for Polymorphism Genotyping."Jpn.J Cancer Res.. 91. 865-868 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakayashiki,N., et al.: "Production of a single-chain variable fragment antibody recognizing type III mutant epidermal growth factor receptor."Jpn.J.Cancer Res.. 91. 1035-1043 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsukamoto,T., et al.: "Development and distribution of 2-Amimo-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced aberrant crypt foci in the rat large intestine."Jpn.J Cancer Res.. 90. 720-725 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Achiwa,H., et al.: "Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas."Clin.Caner Res.. 5. 1001-1005 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Achiwa, H., Yatabe, Y., Hida, T., Kuroishi, T., Kozaki, K., Nakamura, S., Ogawa, M., Sugiura, T., Mitsudomi, T.and Takahashi, T.: "Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas."Clin.Cancer Res.. 5. 1001-1005 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsukamoto, T., Kozaki, K., Nishikawa, Y., Yamamoto, M., Fukami, H., Inoue, M., Wakabayashi, K.and Tatematsu, M.: "Development and distribution of 2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) induced aberrant crypt foci in the rat large intestine."Jpn.J.Cancer Res.. 90. 720-725 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Uemura, H., Nakagawa, Y., Yoshida, K., Saga, S., Yoshikawa, K., Hirao, Y.and Oosterwijk, E.: "MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas."Br.J.Cancer. 81. 741-746 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Azuma, M., Kojima, T., Yokoyama, I., Tajiri, H., Yoshikawa, K., Saga, S.and Del, Carpio, CA.: "Antibacterial activity of multiple antigen peptides homologous to a loop region in human lactoferrin."J.Pept.Res.. 54. 237-241 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoyama, I., Miyazaki, T., Takayama, F., Tsukushi, S., Saga, S., Shimokata, K.and Niwa, T.: "Oral adsorbent ameliorates renal TGF-beta 1 expression in hypercholesterolemic rats."Kidney Int.Suppl.. 71. S193-S197 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kojima, T., Del, Carpio, CA., Tajiri, H., Yoshikawa, K., Saga, S.and Yokoyama, I.: "Inhibition of complement-mediated immune hemolysis by peptides derived from the constant domain of immunoglobulin."Transplantation. 67. 637-638 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kozaki, K., Miyaishi, O., Tsukamoto, T., Tatematsu, T., Hida, T., Takahashi, T.and Takahashi, T.: "Establishment and characterization of a human lung cancer cell line NCI-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation."Cancer Res.. 69. 2535-2540 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hida, T., Kozaki, K., Muramatsu, H., Masuda, A., Shimizu, S., Mitsudomi, T., Sugiura, T., Ogawa, M.and Takahashi, T.: "Cyclooxygenase (COX)-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines."Clin.Cancer Res.. 6. 2006-2011 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hamajima, N., Saito, T., Matsuo, K., Kozaki, K., Takahashi, T., Tajima, K.: "Polymerase Chain Reaction with Confronting Two-pair Primers for Polymorphism Genotyping."Jpn.J.Cancer Res.. 91. 865-868 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakayashiki, N., Yoshikawa, K., Nakamura, K., Hanai, N., Okamoto, K., Okamoto, S., Mizuno, M., Wakabayashi, T., Saga, S., Yoshida, J.and Takahashi, T.: "Production of a single-chain variable fragment antibody recognizing type III mutant epidermal growth factor receptor."Jpn J Cancer Res.. 91. 1035-1043 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Azuma, M., Kojimab, T., Yokoyama, I., Tajiri, H., Yoshikawa, K., Saga, S.and Del, Carpio, CA.: "A synthetic peptide of human apoprotein E with antibacterial activity."Peptides. 21. 327-330 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary

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Published: 1999-04-01   Modified: 2016-04-21  

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