Regulation of aminopeptidase A in human brain tumor vasculature: evidence for a role of transforming growth factor-beta

Détails

ID Serval
serval:BIB_F4CB8E62D27D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Regulation of aminopeptidase A in human brain tumor vasculature: evidence for a role of transforming growth factor-beta
Périodique
Laboratory investigation; a journal of technical methods and pathology
Auteur⸱e⸱s
Juillerat-Jeanneret  L., Lohm  S., Hamou  M. F., Pinet  F.
ISSN
0023-6837 (Print)
Statut éditorial
Publié
Date de publication
2000
Volume
80
Numéro
6
Pages
973-980
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
Angiotensin peptides are potent vasoconstrictors, cell growth factors, and neuromodulators in normal and pathological situations. To assess the potential role of the angiotensins in brain tumor-associated vessels, the expression of the enzymes of the angiotensin cascade were evaluated in these tumors. The production of these bioactive peptides is dependent on the activities of exopeptidases, including several aminopeptidases and carboxypeptidases, producing angiotensin (Ang) I, II, III, IV and Ang 1-7. Human cerebral parenchymal and glioblastoma cells expressed renin, and tumor vasculature, but not glioblastoma cells, expressed angiotensin-converting enzyme. High aminopeptidase A (APA) activity, but no aminopeptidase N/B activity, was observed in human brain tumor vasculature, suggesting a predominant production of Ang III. Grafting of rat glioma cells in rat brains yielded tumors with high APA and low aminopeptidase N/B activities in tumor vessels, confirming human results. Tumor growth and APA activity in tumor vessels were not affected by chronic angiotensin-converting enzyme inhibition. The brain-derived EC219 endothelial cells expressed high APA activity, which was not involved in endothelial cell proliferation, but was down-regulated by exposure of cells to transforming growth factor-beta (TGF beta) or to TGF beta-secreting tumor cells, suggesting a role for this peptide in the control of APA activity in cerebral vasculature. Thus, APA is a potential marker of chronic dysfunction, involving loss of TGF beta function, of the metabolic blood-brain barrier, but not of neovascularization
Mots-clé
Aminopeptidases/metabolism/Angiotensins/physiology/Animals/Brain Neoplasms/blood supply/enzymology/Pathology/Cell Division/Cerebrovascular Circulation/Endothelium,Vascular/drug effects/Glioblastoma/Glutamyl Aminopeptidase/Humans/Neovascularization,Pathologic/Rats/Rats,Inbred F344/Transforming Growth Factor beta/pharmacology
Pubmed
Web of science
Création de la notice
29/01/2008 18:32
Dernière modification de la notice
20/08/2019 16:21
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