Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Antiangiogenic and Antitumor Activities of the Cryptic Fragments with Kringle Architecture

  • Joe, Young-Ae (Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea) ;
  • Kim, Myung-Rae (Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea) ;
  • Shim, Byoung-Shik (Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea) ;
  • Oh, Dae-Shik (Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea) ;
  • Hong, Sung-Hee (Laboratory of Experimental Therapeutics, Korea Institute of Radiological and Medical Sciences) ;
  • Hong, Yong-Kil (Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea)
  • Published : 2003.12.01
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Abstract

Various angiogenesis inhibitors target vascular endothelial cells and block tumor angiogenesis. Angiostatin is a specific endogenous angiogenesis inhibitor in clinical trials, which contains only the first four triple loop structures, known as kringle domains. Its generated by proteolytic cleavage of its parent molecule plasminogen, which itself does not exhibit antiangiogenic activity. Kringle domains from prothrombin, apolipoprotein, hepatocyte growth factor, urokinase and tissue-type plasminogen activator also elicit anti-angiogenic or antitumor activities in several model systems, albeit low amino acid sequence identity between angiostatin and each individual kringle. However, the differential effects of each kringle domain on endothelial cell proliferation, and migration observed in these kringle domains, suggest that the amino acid sequence of the primary structure is still important although kringle architecture is essential for anti-mlgiogenic activity. If it is further studied as to how amino acid sequence and kringle architecture contributes in anti-angiogenic activity, with studies on underlying mechanisms of anti-angiogenesis by kringle-based angiogenesis inhibitors, it will provide basis for the development of new potent anti-angiogenesis inhibitors and improvement of the efficacy of angiogenesis inhibitors.

Keywords

References

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