Recombinant human prothrombin kringle-2 inhibits B16F10 melanoma metastasis through inhibition of neovascularization and reduction of matrix metalloproteinase expression |
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Authors: | Tae Hyong Kim Sookyung Ahn Jaebeum Kim Ilhan Kim Mei Zi Yang Jong Eun Lee Soung Soo Kim |
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Institution: | (1) Department of Biochemistry, College of Science, Yonsei University, Seoul, 120-749, Korea;(2) Department of Anatomy, BK21 project for Medical Sciences, College of Medicine, Yonsei University, Seoul, 120-752, Korea |
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Abstract: | Angiogenesis, a multi-step process which involves endothelial cell proliferation, adhesion, migration, and basement membrane
(BM) degradation, is essential for tumor metastasis. Here we show that recombinant human prothrombin kringle-2 (rk-2) inhibited
bovine capillary endothelial cell migration with an IC50 (concentration for half maximal inhibition) of 38 nM and inhibited adhesion to extracellular matrix (ECM) proteins. Because
tumor metastasis requires angiogenesis, we examined whether rk-2 could inhibit metastases induced by injection of B16F10 melanoma
cells into mice. The results revealed that the metastatic tumors in mouse lung were markedly decreased in a dose-dependent
manner and acute lung injury induced by B16F10 melanoma metastasis was diminished by systemic rk-2 treatment. In immunohistochemical
analysis, rk-2 reduced expression of vascular endothelial growth factor, which is a potent angiogenic activator and neovascularization
in the mouse lung. Also, rk-2 diminished the expression of matrix metalloproteinase-2 and -9 in the mouse lung which induces
tumor metastasis and angiogenesis. These data suggest that inhibition of B16F10 melanoma metastasis by rk-2 was caused by
inhibition of neovascularization and reduction of matrix metalloproteinase expression. |
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Keywords: | Angiogenesis B16F10 melanoma metastasis Immunohistochemistry Matrix metalloproteinase Human prothrombin kringle-2 |
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