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KMID : 0371320010600010001
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Journal of the Korean Surgical Society
2001 Volume.60 No. 1 p.1 ~ p.7
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Inhibition Effect of Angiostatin and Endostatin on Human Angiogenesis
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Jung Sung-Pil
Lee Min-Hyuk
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Abstract
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Purpose: Angiogenesis is a critical determinant of tumor growth and the development of metastasis. Angiostatin and endostatin have been used in a variety of in vitro and in vivo animal models as effective inhibitors of angiogenesis. However, human angiostatin and endostatin have not been tested against an intact human tissue target in vitro to determine its ability to achieve an antiangiogenic response. We performed our study to determine if human angiostatin and endostatin would inhibit the development of an an giogenic response (initiation) and to determine the sub sequent growth (angiogenic index) of human vessels in a dose-dependent manner with a human placental vein angiogenesis model (HPVAM).
Methods: We used full thickness human placental vein discs cultured in three-dimensional fibrin-thrombin clots with an overlay of liquid media. Human angiostatin and endostatin were evaluated in concentrations ranging from 10-9 M to 10-4 M. A positive control containing 20% feta l bovine serum and a negative control using heparin and hydro cortisone 21-phosphate were also tested.
Results: Human angiostatin did not inhibit the initiation of an angiogenic response and the subsequent development of the angiogenic response (angiogenic index) at any concen tration. Human endostatin significantly inhibited the initiation rate of an angiogenic response at a concentration of 10-4 M (p＜0.001) and the subsequent development of an angio genic response (angiogenic index) from a concentrations of 10-5 M to 10-4 M (p＜0.001, p＜0.001, respectively).
Conclusion: We conclude that a very high concentration of human endostatin can inhibit the angiogenic response in human vascular tissue and that human angiostatin will not inhibit angiogenesis of normal human blood vessels in vitro These results suggest that human endostatin has a more powerful antiangiogenic effect than human angiostatin, but we need further investigations of human angiostatin against an intact human tissue target.
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KEYWORD
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Angiostatin, Endostatin, Angiogenesis, Antian giogenesis, Human placental vein angioge nesis model
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