侵袭相关细胞外基质分子在人胶质母细胞瘤与脑内肺腺癌转移中的表达。

Central European Neurosurgery Pub Date : 2010-11-01 Epub Date: 2010-04-15 DOI:10.1055/s-0030-1249698
I Varga, G Hutóczki, M Petrás, B Scholtz, E Mikó, A Kenyeres, J Tóth, G Zahuczky, L Bognár, Z Hanzély, A Klekner
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引用次数: 26

摘要

肿瘤细胞侵入周围脑组织是根治性手术切除失败的主要原因,肿瘤以微播散性疾病的形式复发。细胞外基质(Extracellular matrix, ECM)相关分子及其受体主要参与细胞对周围微环境的粘附和细胞迁移等侵袭过程。恶性肿瘤对健康脑的浸润程度与肿瘤细胞类型密切相关。恶性胶质瘤表现出比转移性肿瘤更强烈的瘤周侵袭。本研究通过定量逆转录-聚合酶链反应研究了30种侵袭相关分子(21种ECM组分、2种相关受体和7种ECM相关酶)的mRNA表达。我们对胶质母细胞瘤(GBM)、脑内肺腺癌转移和正常大脑的新鲜冷冻人体组织样本进行了评估。30个分子中有24个分子存在显著差异。为了在蛋白水平上证实我们的结果,我们对7个分子(agrin、neurocan、syndecan、versican、matrix metalloproteinase 2 [MMP-2]、MMP-9和透明质酸)进行了免疫组织化学分析。确定不同来源肿瘤侵袭相关分子水平的差异有助于确定促进胶质母细胞瘤细胞浸润的确切分子机制。这些结果应该允许选择靶向分子用于针对高度侵袭性恶性胶质瘤的潜在化疗药物。
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Expression of invasion-related extracellular matrix molecules in human glioblastoma versus intracerebral lung adenocarcinoma metastasis.

Tumor cell invasion into the surrounding brain tissue is mainly responsible for the failure of radical surgical resection, with tumor recurrence in the form of microdisseminated disease. Extracellular matrix (ECM)-related molecules and their receptors predominantly participate in the invasion process, including cell adhesion to the surrounding microenvironment and cell migration. The extent of infiltration of the healthy brain by malignant tumors strongly depends on the tumor cell type. Malignant gliomas show much more intensive peritumoral invasion than do metastatic tumors. In this study, the mRNA expression of 30 invasion-related molecules (twenty-one ECM components, two related receptors, and seven ECM-related enzymes) was investigated by quantitative reverse transcriptase-polymerase chain reaction. Fresh frozen human tissue samples from glioblastoma (GBM), intracerebral lung adenocarcinoma metastasis, and normal brain were evaluated. Significant differences were established for 24 of the 30 molecules. To confirm our results at the protein level, immunohistochemical analysis of seven molecules was performed (agrin, neurocan, syndecan, versican, matrix metalloproteinase 2 [MMP-2], MMP-9, and hyaluronan). Determining the differences in the levels of invasion-related molecules for tumors of different origins can help to identify the exact molecular mechanisms that facilitate peritumoral infiltration by glioblastoma cells. These results should allow the selection of target molecules for potential chemotherapeutic agents directed against highly invasive malignant gliomas.

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Central European Neurosurgery
Central European Neurosurgery CLINICAL NEUROLOGY-NEUROSCIENCES
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