基质金属蛋白酶 MMP-1、MMP-11 和 MMP-19 的表达与人恶性胶质瘤的 WHO 分级相关,Neuroscience Research

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基质金属蛋白酶 MMP-1、MMP-11 和 MMP-19 的表达与人恶性胶质瘤的 WHO 分级相关
Neuroscience Research ( IF 2.4 ) Pub Date : 2008-01-01 , DOI: 10.1016/j.neures.2007.09.009
Jelena Stojic ₁ , Carsten Hagemann , Stefanie Haas , Christian Herbold , Siglinde Kühnel , Stefanie Gerngras , Wolfgang Roggendorf , Klaus Roosen , Giles Hamilton Vince

Affiliation

胶质母细胞瘤 (GBM) 是成人中最常见的恶性原发性脑肿瘤类型。它们可能从头出现或从低级别星形细胞瘤 (LGA) 或间变性星形细胞瘤发展而来。它们的特点是侵袭性局部生长模式和显着程度的侵袭性，导致预后不良。蛋白水解酶（例如基质金属蛋白酶 (MMP)）的活性增加会促进肿瘤进展。与 LGA 和正常大脑 (NB) 相比，在胶质母细胞瘤中发现了几种 MMP 的水平升高。然而，一些 MMPs（如 MMP-1）的数据存在争议，其他 MMPs（如 MMP-11 和 MMP-19）尚未详细分析。我们通过半定量 RT-PCR 检测了 MMP-1、MMP-9、MMP-11 和 MMP-19 在 NB、LGA 和 GBM 中的表达，蛋白质印迹和免疫组织化学发现，与 LGA 或 NB 相比，这些 MMP 在 GBM 中的表达增强，在信号强度和显示 MMP 表达的肿瘤百分比方面。从 LGA 到 GBM 的转变的特点是 pro-MMP-11 转变为活性酶的表达。因此，MMP-1、MMP-11 和 MMP-19 可能对高级别星形细胞肿瘤的发展具有重要意义，并且可能是有希望的治疗靶点。

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Expression of matrix metalloproteinases MMP-1, MMP-11 and MMP-19 is correlated with the WHO-grading of human malignant gliomas

Glioblastomas (GBM) are the most prevalent type of malignant primary brain tumor in adults. They may manifest de novo or develop from low-grade astrocytomas (LGA) or anaplastic astrocytomas. They are characterized by an aggressive local growth pattern and a marked degree of invasiveness, resulting in poor prognosis. Tumor progression is facilitated by an increased activity of proteolytic enzymes such as matrix metalloproteinases (MMPs). Elevated levels of several MMPs were found in glioblastomas compared to LGA and normal brain (NB). However, data for some MMPs, like MMP-1, are controversially discussed and other MMPs like MMP-11 and MMP-19 have as yet not been analysed in detail. We examined the expression of MMP-1, MMP-9, MMP-11 and MMP-19 in NB, LGA and GBM by semiquantitative RT-PCR, Western blotting and immunohistochemistry and found an enhanced expression of these MMPs in GBM compared to LGA or NB in signal strength and in the percentage of tumors displaying MMP expression. The transition from LGA to GBM was characterized by a shift of pro-MMP-11 to expression of the active enzyme. Therefore, MMP-1, MMP-11 and MMP-19 might be of importance for the development of high-grade astrocytic tumors and may be promising targets for therapy.

更新日期：2008-01-01

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