Invasiveness of malignant glioma and lipoprotein receptor related protein

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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.