Production and post-surgical modification of VEGF, tPA and PAI-1 in patients with glioma.
Malignant gliomas are associated with risk of thromboembolism, but the molecular link between tumor and peripheral pro-coagulant status has not been elucidated. Vascular Endothelial Growth Factor (VEGF), tissue-type Plasminogen Activator (tPA), Plasminogen Activator Inhibitor-1 (PAI-1) and lipoprotein (lp) (a) influence the pro-coagulant status. To assess whether the presence of the tumor influenced the peripheral levels of VEGF, tPA, PAI-1 and lp(a), we studied the expression and secretion of VEGF, tPA, PAI-1 and lp(a) in glioma specimens, in peripheral blood and in primary glioma-derived cultures. We also measured lp(a), VEGF, tPA and PAI-1 in the peripheral circulation of patients, before and after surgery for glioma. VEGF, tPA and PAI-1 were expressed in glioma specimens. Glioma cells were indeed a major source of tPA and PAI-1; these molecules were significantly more expressed in glioma than in patient's blood cells. Lp(a) was rarely expressed in glioma specimens and not expressed in blood cells. In glioma, VEGF, tPA and PAI-1 were localized mainly in tumor cells; tPA was localized also in the extracellular matrix and PAI-1 in tumor vascular lumen. Glioma cells were indeed able to produce and release VEGF, tPA and PAI-1. After surgery, peripheral levels of VEGF and PAI-1 were increased, while tPA and lp(a) were unchanged. The great amount of VEGF, tPA and PAI-1 produced by glioma could influence peripheral levels of these molecules. The partial resection of the tumor by surgery was not able to decrease plasma levels of these molecules.
Salmaggi
Andrea
A
National Neurological Institute "C. Besta", Milan, Italy.
Croci
Danilo
D
Prina
Paola
P
Cajola
Laura
L
Pollo
Bianca
B
Marras
Carlo E
CE
Ciusani
Emilio
E
Silvani
Antonio
A
Boiardi
Amerigo
A
Sciacca
Francesca L
FL
D001932:Brain Neoplasms / Q000737:chemistry* / Q000150:complications / Q000601:surgery; D005260:Female; D005910:Glioma / Q000737:chemistry* / Q000150:complications / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013927:Thrombosis / Q000175:diagnosis* / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000032:analysis* / Q000097:blood / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000097:blood / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D042461:Vascular Endothelial Growth Factor A; D010959:Tissue Plasminogen Activator