Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human meningiomas.
We studied the expression of vascular endothelial growth factor-A (VEGF-A) and mRNA stability factor HuR in 40 supratentorial meningiomas using RT-PCR, ELISA and immunohistochemistry, and analyzed their associations with the clinicopathological characteristics, including microvascular density (MVD), peritumoral brain edema (PTBE), histological subtypes and grades, and the performance of preoperative arterial embolization. Furthermore, we investigated the involvement of HuR in the upregulation of VEGF-A expression using primary meningioma cell cultures. The level of VEGF-A is elevated in meningiomas with PTBE and in higher grade meningiomas. Preoperative arterial embolization did not significantly increase the level of VEGF-A, but it did increase the expression of HuR in tumor tissues. HuR expression was correlated positively with VEGF-A expression in meningioma tissues. In in vitro experiments, hypoxia induced the upregulation of VEGF-A expression and the cytoplasmic translocation of HuR protein in meningioma cells, and inhibition of the cytoplasmic translocation of HuR reduced the upregulation of VEGF-A expression in meningioma cells. These findings suggest that the expression of VEGF-A relates to the development of PTBE with meningiomas and the histological grade, and that HuR is involved in the upregulation of VEGF-A expression in human meningiomas.
Sakuma
Takahiro
T
Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193, Japan.
Nakagawa
Takao
T
Ido
Kazunori
K
Takeuchi
Hiroaki
H
Sato
Kazufumi
K
Kubota
Toshihiko
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000792:Angiography; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008579:Meningioma / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010100:Oxygen / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D018952:Antigens, CD34; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen; C038753:leptomycin B