Regulation of peptidase activity in a three-dimensional aggregate model of brain tumor vasculature.

Details

Serval ID
serval:BIB_C57E6044ACAE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulation of peptidase activity in a three-dimensional aggregate model of brain tumor vasculature.
Journal
Cell and Tissue Research
Author(s)
Juillerat-Jeanneret L., Monnet-Tschudi F., Zurich M.G., Lohm S., Duijvestijn A.M., Honegger P.
ISSN
0302-766X[print], 0302-766X[linking]
Publication state
Published
Issued date
01/2003
Volume
311
Number
1
Pages
53-59
Language
english
Notes
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The abnormal vascular system of brain cancers inappropriately expresses membrane proteins, including proteolytic enzymes, ultimately resulting in blood extravasation. The production of inflammatory mediators, such as cytokines and nitric oxide, and tumor hypoxia have been implicated in these effects. We have previously shown that the activity of aminopeptidase A is increased in the abnormal vascular system of human and rat brain tumors. To study the mechanisms regulating the activities of peptidases in cerebral vasculature in brain tumors, we have developed a three-dimensional model of differentiated rat brain cells in aggregate cultures in which rat brain microvessels were incorporated. The secretion of interleukin-6 (IL-6) in the culture medium of aggregates was used as an indicator of inflammatory activation. Addition to these aggregates of C6 glioma cell medium (C6-CM) conditioned under hypoxic or normoxic conditions or serum mimicked tumor-dependent hypoxia or conditions of dysfunction of brain tumor vasculature. Hypoxic and normoxic C6-CM, but not serum, regulated peptidase activity in aggregates, and in particular it increased the activity of aminopeptidase A determined using histoenzymography. Serum, but not C6-CM, increased IL-6 production, but did not increase aminopeptidase A activity in aggregates. Thus soluble glioma-derived factors, but not serum-derived factors, induce dysfunctions of cerebral vasculature by directly regulating the activity of peptidases, not involving inflammatory activation. Tumor hypoxia is not necessary to modulate peptidase activity.
Keywords
Aminopeptidases/metabolism, Animals, Brain Neoplasms, Cell Aggregation, Cell Differentiation, Cell Hypoxia, Culture Media, Conditioned, Female, Glioblastoma, Glutamyl Aminopeptidase, Neovascularization, Pathologic/enzymology, Pregnancy, Rats, Solubility, Tumor Cells, Cultured/enzymology
Pubmed
Web of science
Create date
24/01/2008 13:11
Last modification date
20/08/2019 15:41
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