Analysis of VEGF, Flt-1, Flk-1, nestin and MMP-9 in relation to astrocytoma pathogenesis and progression.
Analysis of VEGF, Flt-1, Flk-1, nestin and MMP-9 in relation to astrocytoma pathogenesis and progression.
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DOI：
10.4149/neo_2009_04_284
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发表时间：
2009-01-01
期刊：
影响因子：
3
通讯作者：
Kolar, Z.
中科院分区：
文献类型：
--
作者：
Hlobilkova, A.;Ehrmann, J.;Kolar, Z.
星形细胞瘤，尤其是高级别星形细胞瘤，是一种具有强血管生成活性的脑肿瘤。我们的免疫组织化学研究评估了血管内皮生长因子（VEGF）、VEGF受体（Flk-1和Flt-1）、在中枢神经系统发育中起作用的中间丝状蛋白巢蛋白，以及与肿瘤侵袭和血管生成调节有关的基质金属蛋白酶家族的MMP-9。我们研究了VEGF及其受体、巢蛋白和MMP-9在星形细胞瘤中的表达及其与肿瘤分级的关系。我们使用了66例患者的石蜡包埋样本，其中29例为低级别（who分级11级），37例为高级别（who分级III级和IV级）星形细胞瘤。使用抗VEGF、Flk-1、Flt-1、nestin、CD34和MMP-9抗体，然后采用标准间接免疫组织化学方法。Flt-1和Flk-1的表达在低、高分级肿瘤组间无显著差异。高分级组VEGF、MMP-9表达升高（p分别小于等于0.026、0.024）。高分级组肿瘤星形细胞和内皮细胞中Nestin表达升高（p = 0.007和0.003）。VEGF在高级别星形细胞瘤中的高表达可能导致存活、血管生成和迁移的激活。nestin和MMP-9的表达也提示它们可能在星形细胞瘤血管发育和增殖中起作用。
Astrocytomas, particularly high grade astrocytoma, are brain tumors with potent angiogenic activity. Our immnunohistochemical study assessed vascular endothelial growth factor (VEGF), VEGF receptors (Flk-1, and Flt-1), the intermediate filamental protein nestin which plays a role in central nervous system development, and MMP-9, which belongs the family of matrix metalloproteinases implicated in tumor invasion and angiogenesis regulation. We investigated the expression of VEGF, its receptors, nestin and MMP-9 in astrocytomas and their correlation with tumor grade. We used paraffin-embedded samples from 66 patients, 29 with low grade (WHO-grade 11) and 37 with high grade (WHO-grade III and IV) astrocytomas. Antibodies against VEGF, Flk-1, Flt-1, nestin, CD34 and MMP-9 were used, followed by standard indirect immunohistochemical methods. Expression of Flt-1 and Flk-1 showed no significant differences between low and high grade tumor groups. Expression of VEGF and MMP-9 was increased in the high grade group (p equal to or less than 0.026 and 0.024). Nestin expression in tumor astrocytes and endothelial cells increased in high grade group (p same 0.007 and 0.003). Higher expression of VEGF in high grade astrocytomas may subsequently lead to activation of survival, angiogenesis and migration. Expression of nestin and MMP-9 also suggest their likely role in astrocytoma vascular development and proliferation.