Increased expression of low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor in human malignant astrocytomas.

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 PCR and immunohistochemical analysis. LRP mRNA was expressed frequently in glioblastomas, as compared with low-grade astrocytomas by PCR analysis and was well correlated with uPAR expression. These results were consistent with the immunohistochemical localization of LRP in glioblastomas. Immunohistochemistry of LRP on sequential frozen sections showed that neoplastic glial cells and endothelial cells of glioblastomas exhibited intense LRP immunoreactivity, whereas LRP was almost undetectable in low-grade astrocytomas and in normal glial cells and endothelial cells of normal brain tissues. In normal brain tissues, LRP immunoreactivity was identified in the pyramidal neurons of the cerebral cortex. In metastatic brain tumors (metastatic lung adenocarcinomas) and primary lung adenocarcinomas, LRP expression was low to undetectable, suggesting that LRP expression is regulated differently in these tumors than in malignant astrocytomas. 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 suggest strongly that LRP may play a role in facilitating glioblastoma invasiveness and neovascularization within tumor tissues by regulating cell surface proteolytic activity.