The human Fn14 receptor gene is up-regulated in migrating glioma cells in vitro and overexpressed in advanced glial tumors.
Glioblastoma multiforme comprises the majority of human brain tumors. Patients with glioblastoma multiforme have poor survival rates, with an average life expectancy of <1 year. To assess possible mechanisms and to potentially target invasive glioma cells, we previously measured the gene expression profiles of glioma cells under migration-activated or passive states. One of the genes identified was Fn14, which encodes a cell surface receptor for the tumor necrosis factor superfamily member named TWEAK. In this study, we show that Fn14 gene expression is induced in migration-activated glioma cells in vitro and significantly increases according to tumor grade in vivo (P < 0.01), with highest levels in glioblastoma tissue specimens. The in situ expression pattern of Fn14 mRNA and protein was confined to primary glioma cells and the vascular endothelium, with no detection in adjacent normal brain. Conversely, TWEAK mRNA levels are low in glioblastoma samples relative to normal brain tissue. In addition, activation of the Fn14 receptor by addition of recombinant TWEAK resulted in increased glioma cell migration in vitro. These results suggest a positive role for TWEAK and Fn14 in glioma progression and indicate that Fn14 gene expression may serve as a marker for invasive glioma cells.
Tran
Nhan L
NL
Neuro-Oncology Research, Barrow Neurological Institute, Phoenix, Arizona, USA.
McDonough
Wendy S
WS
Donohue
Patrick J
PJ
Winkles
Jeffrey A
JA
Berens
Theresa J
TJ
Ross
Kristen R
KR
Hoelzinger
Dominique B
DB
Beaudry
Christian
C
Coons
Stephen W
SW
Berens
Michael E
ME
D051017:Apoptosis Regulatory Proteins; D001254:Astrocytoma; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics*; D002465:Cell Movement; D002470:Cell Survival; D000074049:Cytokine TWEAK; D004730:Endothelium, Vascular / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D017403:In Situ Hybridization; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D000074049:Cytokine TWEAK; D012333:RNA, Messenger; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors