Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cells

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Cambados, Nadia
Walther, Thomas
Nahmod, Karen
Tocci, Johanna M.
Rubinstein, Natalia
Boehme, Ilka
Simian, Marina
Sampayo, Rocio
Del Valle Suberbordes, Melisa
Kordon, Edith C.
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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.
AKT , Angiotensin ii , Angiotensin-(1-7) , Breast cancer cells , Epithelial-mesenchymal transition
Cambados, N., Walther, T., Nahmod, K., Tocci, J. M., Rubinstein, N., Böhme, I., Simian, M., Sampayo, R., Suberbordes, M. D. V. and Kordon, E. C. (2017) 'Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cells', Oncotarget, 8(51), pp. 88475-88487. doi: 10.18632/oncotarget.19290