Expression of endothelin 1 and its angiogenic role in meningiomas.
Meningiomas are one of the most frequent central nervous system tumours. Although slow-growing at times, they continue to be a cause of morbidity and mortality. The endothelin (ET) family consists of three isoforms: ET-1 is the most abundant one. ET-1 may be involved in meningioma tumourigenesis in concert with other growth factors, in particular with angiogenic agents. We analysed ET-1 expression by immunohistochemistry and its activating system by reverse-transcription-polymerase chain reaction in 56 cases of meningioma. We found an association between high-grade meningiomas and high ET-1 expression levels (p=0.002). Moreover, we evaluated the potential angiogenic role of ET-1, finding an elevated microvessel count in tumours with high ET expression levels (p=0.004). ET-1 may contribute to meningioma growth by inducing formation of new blood vessels. The finding that ET-1 expression positively correlates with vascular endothelial growth factor (VEGF) expression in meningiomas (p=0.03) also supports the hypothesized modulating effect of ET-1 on angiogenesis. Thus, the influence of the ET system on the progression of meningiomas may occur through stimulation of VEGF. The association of ET-1 and meningioma represents a potential area for therapeutic intervention with selective ET inhibitors. Additional clinical studies will be needed before inhibitors can be incorporated in clinical practice.
Boldrini
Laura
L
Department of Surgery, University of Pisa, via Roma 57, 56100 Pisa, Italy. l.boldrini@med.unipi.it
Pistolesi
Sabina
S
Gisfredi
Silvia
S
Ursino
Silvia
S
Alì
Greta
G
Pieracci
Nicola
N
Basolo
Fulvio
F
Parenti
Giuliano
G
Fontanini
Gabriella
G
D000328:Adult; D000368:Aged; D019332:Endothelin-1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008577:Meningeal Neoplasms / Q000098:blood supply* / Q000473:pathology; D008579:Meningioma / Q000098:blood supply* / Q000473:pathology; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D019332:Endothelin-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A