Invasiveness of malignant glioma and lipoprotein receptor related protein

低密度脂蛋白受体相关蛋白（LRP）在调节蛋白酶活性方面起重要作用，而蛋白酶活性是细胞侵袭过程所必需的。在这项研究中，我们调查了存在的LRP和尿激酶型纤溶酶原激活物受体（uPAR）在星形细胞瘤组织和胶质瘤细胞系的聚合酶链反应和免疫组化分析。LRP mRNA在胶质母细胞瘤中频繁表达，与低级别星形细胞瘤相比，通过聚合酶链反应分析，并与uPAR表达相关。这些结果与LRP蛋白在胶质母细胞瘤中的免疫组化定位一致。LRP免疫组化结果显示，胶质母细胞瘤的肿瘤胶质细胞和内皮细胞显示出强烈的LRP免疫反应性，而LRP在低级别星形细胞瘤或正常脑组织的正常胶质细胞和内皮细胞中几乎检测不到。在正常脑组织中，LRP免疫反应性被确定在她的地方。将LRP cDNA转染不表达LRP的U105 MG细胞株，Matrigel体外侵袭实验显示LRP阳性的U105 MG（U105 MG LRP+）细胞的侵袭能力较U105 MG细胞增强。这些结果表明，LRP在恶性星形细胞瘤，特别是胶质母细胞瘤中过度表达，并且LRP的表达增加似乎与uPAR的表达和星形细胞瘤的恶性程度相关。我们的研究结果强烈表明，LRP可能通过调节细胞表面蛋白水解活性，在促进胶质母细胞瘤的侵袭和肿瘤组织内的新生血管形成中发挥作用。

Low density lipoprotein receptor-related protein (LRP) plays an important role in regulating proteinase activity, which is necessary for cellular invasive processes. In this study, we investigated the presence of both LRP and urokinase-type plasminogen activator receptor (uPAR) in astrocytoma tissues and in glioma cell lines by polymerase chain reaction and immunohistochemical analysis. LRP mRNA was frequently expressed in glioblastomas, as compared with low-grade astrocytomas by polymerase chain reaction analysis, and was correlated with uPAR expression. These results were consistent with the immunohistochemical localization of LRP protein in glioblastomas. Immunohistochemistry of LRP on sequential frozen sections showed that neoplastic glial cells and endothelial cells of glioblastomas exhibited intense LRP immunoreactivity, while LRP was almost undetectable in low-grade astrocytomas, or in normal glial cells and endothelial cells of normal brain tissues. In normal brain tissues, LRP immunoreactivity was identified in her places.ebral cortex. U105MG cell line, which did not express LRP, was transfected LRP cDNA.This LRP positive U1O5MG (U1O5MG LRP+) showed increased invasiveness compared with U105MG by Matrigel in vitro invasion assay. These results indicate that LRP is overexpressed in malignant astrocytomas, especially in glioblastomas, and the increased expression of LRP appears to correlate with the expression of uPAR and the malignancy of astrocytomas. Our results strongly suggest that LRP may play a role in facilitating glioblastoma invasiveness and neovascularization within tumor tissues by regulating cell surface proteolytic activity.