Abstract
Herein we continue the study of matrix metalloproteinase-1 (MMP-1) with respect to glioblastoma multiforme (GBM) cell tumorigenicity and angiogenesis. A model of tumorigenicity with cells stably altered to over-express or knock-down MMP-1 revealed that it significantly increases tumor incidence and size. Organized endothelial growth in human umbilical vein endothelial cell (HUVEC)-GBM co-cultures was significantly increased in the presence of MMP-1. CD31 analysis of model tumors elucidated a substantial recruitment of endothelium in MMP-1 enhanced samples. Antibody arrays indicated an inverse expression of certain anti-angiogenic factors with respect to MMP-1, the most notable of which was a significant increase in tissue inhibitor of metalloproteinases-4 (TIMP-4) in the absence of MMP-1, as validated by immunoblot.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain Neoplasms / genetics*
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Cell Line, Tumor
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Cell Transformation, Neoplastic / genetics
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Coculture Techniques
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Disease Models, Animal
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Endothelial Cells / pathology
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Gene Expression Regulation, Neoplastic / genetics*
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Glioblastoma / genetics*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Humans
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Matrix Metalloproteinase 1 / genetics*
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Matrix Metalloproteinase 1 / metabolism
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Mice
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Mice, Nude
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Mutation / genetics
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Neovascularization, Pathologic / genetics
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
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Proteomics
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Tissue Inhibitor of Metalloproteinase-4
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Tissue Inhibitor of Metalloproteinases / genetics
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Tissue Inhibitor of Metalloproteinases / metabolism*
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Umbilical Veins / cytology
Substances
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Platelet Endothelial Cell Adhesion Molecule-1
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Tissue Inhibitor of Metalloproteinases
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Green Fluorescent Proteins
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Matrix Metalloproteinase 1