Up-regulation of urokinase and urokinase receptor genes in malignant astrocytoma.
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 alpha nu beta 3 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.
Gladson
C L
CL
Department of Pathology, University of Alabama at Birmingham 35294-0007, USA.
Pijuan-Thompson
V
V
Olman
M A
MA
Gillespie
G Y
GY
Yacoub
I Z
IZ
D000818:Animals; D001254:Astrocytoma / Q000378:metabolism*; D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000378:metabolism*; D002460:Cell Line; D018076:DNA, Complementary / Q000032:analysis; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D014158:Transcription, Genetic / Q000235:genetics; D014183:Transplantation, Heterologous / Q000276:immunology; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D018076:DNA, Complementary; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator