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 |
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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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