Inhibition of endothelial cell proliferation by the recombinant kringle domain of tissue-type plasminogen activator |
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Authors: | Kim Hyun-Kyung Lee Soo Young Oh Ho-Kyun Kang Byoung-Hak Ku Hyeun-Ju Lee Yoon Shin Joo-Young Hong Yong-Kil Joe Young Ae |
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Institution: | Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea, 137-701, Seoul, Republic of Korea |
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Abstract: | Tissue-type plasminogen activator (tPA) is a multidomain serine protease that converts the zymogen plasminogen to plasmin. tPA contains two kringle domains which display considerable sequence identity with those of angiostatin, an angiogenesis inhibitor. TK1-2, a recombinant kringle domain composed of t-PA kringles 1 and 2 (Ala(90)-Thr(263)), was produced by both bacterial and yeast expression systems. In vitro, TK1-2 inhibited endothelial cell proliferation stimulated by basic fibroblast growth factor, vascular endothelial growth factor, and epidermal growth factor. It did not inhibit proliferation of non-endothelial cells. TK1-2 also inhibited in vivo angiogenesis in the chick embryo chorioallantoic membrane model. These results suggest that the recombinant kringle domain of t-PA is a selective inhibitor of endothelial cell growth and identifies this molecule as a novel anti-angiogenic agent. |
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Keywords: | Angiogenesis Tissue-type plasminogen activator Kringle Inhibitor Proliferation |
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