Pulse treatment of human vascular endothelial cells with high doses of tumor necrosis factor and interferon-gamma results in simultaneous synergistic and reversible effects on proliferation and morphology

Details

Serval ID
serval:BIB_6196BC609FB9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pulse treatment of human vascular endothelial cells with high doses of tumor necrosis factor and interferon-gamma results in simultaneous synergistic and reversible effects on proliferation and morphology
Journal
International Journal of Cancer
Author(s)
Yilmaz  A., Bieler  G., Spertini  O., Lejeune  F. J., Ruegg  C.
ISSN
0020-7136 (Print)
Publication state
Published
Issued date
08/1998
Volume
77
Number
4
Pages
592-599
Language
english
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Aug 12
Abstract
Regional administration of high doses of tumor necrosis factor (TNF), interferon gamma (IFNgamma) and melphalan to patients with advanced cancers of the limbs, results in rapid and specific tumor necrosis, while the normal adjacent tissues remain unaffected. The tumor vasculature is selectively destroyed by this treatment, and neovascular endothelial cells appear to be an early and specific target of TNF and IFNgamma. To further understand some of the cellular events underlying these in vivo effects, we have investigated the response of human macro- and microvascular endothelial cells in vitro, after exposure to high doses of TNF and IFNgamma (up to 40 x 10(3) U/ml each). TNF and IFNgamma synergistically inhibited endothelial-cell proliferation by up to 80% after 72 hr of treatment. Achievement of synergy required the simultaneous presence of both cytokines. A cytokine pulse as short as 30 min was sufficient to induce maximal growth inhibition measured after 48 hr. Both cytokines also induced progressive and dose-dependent elongation of the endothelial-cell morphology. The effects on endothelial-cell proliferation and morphology were reversible upon removal of the cytokines. Moreover, replating of treated cells onto a fresh substrate immediately resulted in re-acquisition of their normal shape. In contrast to the effect on cell proliferation, there was little or no effect on the rate of endothelial-cell apoptosis. The presented data extend reports on the effects of TNF and IFNgamma on human endothelial cells in vitro, and suggest that the in vivo disruption of the tumor vasculature caused by high doses of TNF and IFNgamma is not due to a direct cytotoxic effect on endothelial cells but occurs through an indirect mechanism.
Keywords
*Apoptosis Cell Division/drug effects Cell Line/drug effects Drug Synergism Endothelium, Vascular/cytology/*drug effects Humans Interferon Type II/administration & dosage/*pharmacology Tumor Necrosis Factor-alpha/administration & dosage/*pharmacology
Pubmed
Web of science
Create date
28/01/2008 8:36
Last modification date
20/08/2019 14:18
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