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

Details

Serval ID
serval:BIB_F4CB8E62D27D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulation of aminopeptidase A in human brain tumor vasculature: evidence for a role of transforming growth factor-beta
Journal
Laboratory investigation; a journal of technical methods and pathology
Author(s)
Juillerat-Jeanneret  L., Lohm  S., Hamou  M. F., Pinet  F.
ISSN
0023-6837 (Print)
Publication state
Published
Issued date
2000
Volume
80
Number
6
Pages
973-980
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
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
Keywords
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
Create date
29/01/2008 18:32
Last modification date
20/08/2019 16:21
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