Tumoral angiogenesis and tissue factor expression during hepatocellular carcinoma progression in a transgenic mouse model.

Details

Serval ID
serval:BIB_E319D41AEAC4
Type
Article: article from journal or magazin.
Collection
Publications
Title
Tumoral angiogenesis and tissue factor expression during hepatocellular carcinoma progression in a transgenic mouse model.
Journal
Journal of Hepatology
Author(s)
Dupuy E., Hainaud P., Villemain A., Bodevin-Phèdre E., Brouland J.P., Briand P., Tobelem G.
ISSN
0168-8278 (Print)
ISSN-L
0168-8278
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
38
Number
6
Pages
793-802
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
BACKGROUND/AIMS: The hypervascularity described in hepatocellular carcinoma varies according to the progression and the differentiation of the tumor, suggesting an angiogenic switch during tumor development.
METHODS: We used a transgenic mouse model of hepatocellular carcinoma induced by the expression of SV40-T antigen, in which male mice developed hepatic tumors at various temporal and histological stages, whereas female mice remained tumor-free. We analyzed, by immunostaining and reverse transcription-polymerase chain reaction, factors involved in tumoral angiogenesis.
RESULTS: We demonstrated that tumoral angiogenesis occurred before the development of diffuse hepatocarcinoma. We showed that some SV40-T-positive cells with an endothelial phenotype are involved in angiogenic processes, suggesting a partial vasculogenic mimicry. This tumoral angiogenesis is associated with platelet activation due to tissue factor expression in endothelial cells and invading macrophages. Normal and transgenic livers exhibited different pattern of expression of hypoxia-inducible factor 1 alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) mRNA.
CONCLUSIONS: This model of hepatocellular carcinoma displays marked tumoral angiogenesis, with proliferation, remodeling and arterialization of hepatic sinusoids, probably associated with a partial vasculogenic mimicry. Abnormal angiogenesis observed in hepatocarcinoma was associated with platelet activation by tissue factor (TF) produced by endothelial cells and invading macrophages. In this transgenic model, HIF-1alpha, VEGF, and TF play a crucial role in tumoral angiogenesis.
Keywords
Animals, Carcinoma, Hepatocellular/blood supply, Carcinoma, Hepatocellular/metabolism, Disease Progression, Female, Hypoxia-Inducible Factor 1, alpha Subunit, Liver Neoplasms/blood supply, Liver Neoplasms/metabolism, Male, Mice, Mice, Transgenic, Neovascularization, Pathologic/blood, Neovascularization, Pathologic/metabolism, Platelet Activation, RNA, Messenger/metabolism, Thromboplastin/metabolism, Tissue Distribution, Transcription Factors/genetics, Vascular Endothelial Growth Factor A/genetics
Pubmed
Web of science
Create date
13/10/2015 9:35
Last modification date
20/08/2019 16:06
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