Matrix metalloproteinase-1 expression enhances tumorigenicity as well as tumor-related angiogenesis and is inversely associated with TIMP-4 expression in a model of glioblastoma

基质金属蛋白酶-1 表达增强了致瘤性以及肿瘤相关的血管生成,并且在胶质母细胞瘤模型中与 TIMP-4 表达呈负相关

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作者:Nicholas A Pullen, Monika Anand, Patricia S Cooper, Helen L Fillmore

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.

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