Up-regulation of urokinase and urokinase receptor genes in malignant astrocytoma

Academic Article

Abstract

  • To understand the role of urokinase (u-PA) and the urokinase receptor (u- PAR) in malignant astrocytoma cell invasion of normal brain, astrocytic expression of u-PAR and u-PA mRNAs were analyzed by riboprobe in situ hybridization in astrocytoma and non-neoplastic brain biopsies. In eight of eight malignant astrocytomas (glioblastomas), u-PAR and u-PA mRNA expression was demonstrated, whereas in seven non-neoplastic brain biopsies, u-PAR and u-PA mRNAS were not expressed. In one of four low grade and all anaplastic astrocytomas u-PAR mRNA was expressed, although u-PA mRNA was undetectable. Consistent with the mRNA detection, u-PAR and u-PA proteins were expressed by malignant astrocytes in five of five glioblastoma biopsies. To study the tumor margin, U-251MG glioblastoma cells were propagated intracerebrally in a severe combined immunodeficient mouse xenograft (28 days), and u-PA mRNA was found to localize predominantly to the leading tumor edge, whereas u-PAR mRNA was expressed throughout the tumor. Furthermore, adherent human U-251MG glioblastoma cells in vitro expressed u-PAR and u-PA proteins, which localized to sites of integrin αvβ3 cell-matrix contacts. These data indicate that co-expression of u-PAR and u-PA mRNAs and proteins marks the malignant astrocyte phenotype and that u-PA bound to u-PAR may play a role in glioblastoma cell invasion of normal brain by virtue of its expression at the leading tumor edge.
  • Published In

    Author List

  • Gladson CL; Pijuan-Thompson V; Olman MA; Gillespie GY; Yacoub IZ
  • Start Page

  • 1150
  • End Page

  • 1160
  • Volume

  • 146
  • Issue

  • 5