Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cells
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Nadia Cambados1, Thomas Walther2,4,5, Karen Nahmod6, Johanna M. Tocci1, Natalia Rubinstein1,7, Ilka Böhme2,3, Marina Simian8, Rocío Sampayo8, Melisa Del Valle Suberbordes1, Edith C. Kordon1,9 and Carolina Schere-Levy1
1Instituto de Fisiología, Biología Molecular y Neurociencias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
2Department of Obstetrics, University of Leipzig, Leipzig, Germany
3Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany
4Department Pharmacology and Therapeutics, School of Medicine and School of Pharmacy, University College Cork, Cork, Ireland
5Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany
6Department of Pediatrics, Immunology, Allergy and Rheumatology, Center for Human Immunobiology, Texas Children’s Hospital, Houston, Texas, USA
7Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
8Instituto de Nanosistemas, Universidad Nacional de San Martín, Buenos Aires, Argentina
9Departmento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Carolina Schere-Levy, email: firstname.lastname@example.org
Keywords: AKT, angiotensin II, angiotensin-(1-7), breast cancer cells, epithelial–mesenchymal transition
Received: November 04, 2016 Accepted: June 02, 2017 Published: July 17, 2017
Angiotensin (Ang) II, the main effector peptide of the renin-angiotensin system, has been implicated in multiple aspects of cancer progression such as proliferation, migration, invasion, angiogenesis and metastasis. Ang-(1-7), is a biologically active heptapeptide, generated predominantly from AngII by the enzymatic activity of angiotensin converting enzyme 2. Previous studies have shown that Ang-(1-7) counterbalances AngII actions in different pathophysiological settings. In this study, we have analysed the impact of Ang-(1-7) on AngII-induced pro-tumorigenic features on normal murine mammary epithelial cells NMuMG and breast cancer cells MDA-MB-231. AngII stimulated the activation of the survival factor AKT in NMuMG cells mainly through the AT1 receptor. This PI3K/AKT pathway activation also promoted epithelial–mesenchymal transition (EMT). Concomitant treatment of NMuMG cells with AngII and Ang-(1-7) completely abolished EMT features induced by AngII. Furthermore, Ang-(1-7) abrogated AngII induced migration and invasion of the MDA-MB-231 cells as well as pro-angiogenic events such as the stimulation of MMP-9 activity and VEGF expression. Together, these results demonstrate for the first time that Ang-(1-7) counteracts tumor aggressive signals stimulated by AngII in breast cancer cells emerging the peptide as a potential therapy to prevent breast cancer progression.
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