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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Angiopoietin-2 induces human glioma invasion through the activation of matrix metalloprotease-2.
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Angiopoietin-2 induces human glioma invasion through the activation of matrix metalloprotease-2.

机译：血管生成素2通过激活基质金属蛋白酶2诱导人神经胶质瘤浸润。

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摘要

A hallmark of highly malignant human gliomas is their infiltration of the brain. We analyzed a large number of primary human glioma biopsies and found high levels of expression of an angiogenic regulator, angiopoietin-2 (Ang2), in the invasive areas, but not in the central regions, of those tumors. In the invasive regions where Ang2 was overexpressed, increased levels of matrix metalloprotease-2 (MMP-2) were also apparent. Consonant with these features, intracranial xenografts of glioma cells engineered to express Ang2 were highly invasive into adjacent brain parenchyma compared with isogenic control tumors. In regions of the Ang2-expressing tumors that were actively invading the brain, high levels of expression of MMP-2 and increased angiogenesis were also evident. A link between these two features was apparent, because stable expression of Ang2 by U87MG cells or treatment of several glioma cell lines with recombinant Ang2 in vitro caused activation of MMP-2 and acquisition of increased invasiveness. Conversely, MMP inhibitors suppressed Ang2-stimulated activation of MMP-2 and Ang2-induced cell invasion. These results suggest that Ang2 plays a critical role in inducing tumor cell infiltration, and that this invasive phenotype is caused by activation of MMP-2.
机译：高度恶性的人类神经胶质瘤的标志是它们对大脑的浸润。我们分析了许多原发性人脑胶质瘤活检组织，发现在这些肿瘤的浸润区域而不是中部区域，血管生成调节因子Angiopoietin-2（Ang2）的表达水平很高。在Ang2过表达的浸润区域中，基质金属蛋白酶-2（MMP-2）的水平也明显升高。与这些特征相一致，与等基因对照肿瘤相比，经工程改造以表达Ang2的神经胶质瘤细胞的颅内异种移植物对邻近的脑实质具有高度侵袭性。在活跃地侵袭大脑的表达Ang2的肿瘤区域，MMP-2的高水平表达和血管生成的增加也很明显。这两个特征之间的联系是显而易见的，因为U87MG细胞稳定表达Ang2或在体外用重组Ang2处理几种神经胶质瘤细胞系会引起MMP-2活化并增加侵袭性。相反，MMP抑制剂抑制Ang2刺激的MMP-2激活和Ang2诱导的细胞侵袭。这些结果表明，Ang2在诱导肿瘤细胞浸润中起关键作用，并且该侵袭性表型是由MMP-2的激活引起的。

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