title: Angiotensinogen delays angiogenesis and tumor growth of hepatocarcinoma in transgenic mice.
abstract: Angiotensinogen, a member of the serpin family, is involved in the suppression of tumor growth and metastasis. To investigate whether human angiotensinogen protects against tumor progression in vivo, we established an original bitransgenic model in which transgenic mice expressing human angiotensinogen (Hu-AGT-TG mice) were crossed with a transgenic mouse model of hepatocellular carcinoma (HCC-TG mice). Bitransgenic mice overexpressing human angiotensinogen (HCC/Hu-AGT-TG) had a significantly longer survival time than the HCC-TG mice and a reduction of both tumor growth and blood flow velocities in the liver. This antitumor effect of angiotensinogen is related to a reduced angiogenesis, impaired expression of endothelial arterial markers (active Notch4, Delta-like 4 ligand, and ephrin B2) with a decrease of arterial vessel density in HCC/Hu-AGT-TG mice liver. Overexpression of human angiotensinogen decreases angiogenesis, and prevents tumor sinusoids from remodeling and arterialization, thus delaying tumor progression in vivo.
authors.affiliation: Chaire de Médecine Expérimentale, INSERM U833, Collège de France, Paris, France. francois.vincent@college-defrance.fr
authors.forename: François
authors.initials: F
authors.lastname: Vincent
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
authors.forename: Maud
authors.initials: M
authors.lastname: Clemessy
authors.forename: Jean-Olivier
authors.initials: JO
authors.lastname: Contrerès
authors.forename: Noël
authors.initials: N
authors.lastname: Lamandé
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Gasc
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.forename: Patricia
authors.initials: P
authors.lastname: Hainaud
authors.forename: Gérard
authors.initials: G
authors.lastname: Tobelem
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.forename: Evelyne
authors.initials: E
authors.lastname: Dupuy