Suppression of angiogenesis, tumor growth, and metastasis by adenovirus-mediated gene transfer of human angiotensinogen

Autor: Elisabeth Connault, Gabrielle Faure, Pierre Corvol, Jean-Marie Gasc, Michel Perricaudet, Noël Lamandé, Céline Bouquet, Paule Opolon, Betsy Jullienne, Marcus Brand, Franck Griscelli
Přispěvatelé: Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Angiogenesis
Angiotensinogen
Melanoma
Experimental

MESH: Neoplasm Metas
Metastasis
Neovascularization
Mice
0302 clinical medicine
Cell Movement
Drug Discovery
MESH: Endothelial Cells
MESH: Animals
Neoplasm Metastasis
MESH: Cell Movement
Tube formation
0303 health sciences
Neovascularization
Pathologic

Melanoma
Gene Transfer Techniques
MESH: Adenoviridae
3. Good health
Endothelial stem cell
MESH: Melanoma
Experimental

030220 oncology & carcinogenesis
Molecular Medicine
MESH: Endothelium
Vascular

medicine.symptom
medicine.medical_specialty
Transplantation
Heterologous

Mice
Nude

MESH: Angiotensinogen
MESH: Gene Transfer Techniques
Biology
Adenoviridae
03 medical and health sciences
In vivo
MESH: Mice
Inbred C57BL

Internal medicine
MESH: Cell Proliferation
Genetics
medicine
MESH: Mice
Nude

Animals
Humans
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]

Molecular Biology
MESH: Mice
Cell Proliferation
030304 developmental biology
Pharmacology
MESH: Humans
Endothelial Cells
Genetic Therapy
Neoplasms
Experimental

medicine.disease
Angiotensin II
Mice
Inbred C57BL

MESH: Hela Cells
Endocrinology
Cancer research
Endothelium
Vascular

MESH: Gene Therapy
Neoplasm Transplantation
HeLa Cells
Zdroj: Molecular Therapy
Molecular Therapy, Cell Press, 2006, 14 (2), pp.175-82. ⟨10.1016/j.ymthe.2006.01.017⟩
ISSN: 1525-0016
1525-0024
DOI: 10.1016/j.ymthe.2006.01.017⟩
Popis: International audience; Angiogenesis is essential for tumor growth and metastatic dissemination. We have previously shown that human angiotensinogen (AGT) can in vitro inhibit endothelial cell proliferation and migration, capillary-like tube formation, and neovascularization. To determine whether AGT can exert an antitumoral effect through its antiangiogenic properties, we constructed a recombinant adenovirus carrying the human angiotensinogen gene under the control of the cytomegalovirus promoter (AdAGT). In vitro studies showed that AdAGT selectively inhibited endothelial cell proliferation. In vivo, injections of AdAGT into preestablished human MDA-MB-231 mammary carcinomas in nude mice inhibited tumor growth by 70% compared to controls, with 21% total regression. This effect was associated with the suppression of intratumoral vascularization and marked necrosis. Furthermore, in vitroAdAGT infection of MDA-MB-231 and murine melanoma B16F10 cells strongly blocked their in vivo tumorigenicity. Then, in mice expressing high levels of AGT (i.e., either iv injected with AdAGT or HuAGT transgenic mice), the number of B16F10 pulmonary metastases was 85% lower than in control C57BL/6 mice. Our data demonstrate that AGT is a very potent antiangiogenic factor in vivo, independent of angiotensin II generation. Its delivery by gene transfer represents a promising new strategy to block primary tumor growth and to prevent metastasis.
Databáze: OpenAIRE
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