I. Angiotensin II and breast cancer metastasis
Cancer metastasis is considered to be an inefficient process. Among thousands of cancer cells reaching the bloodstream, only few will cross the vascular barrier and colonize distant organs. We showed that AngII, a vasoactive peptide produced both in the circulation and locally in breast tumors, can directly activate cancer cells to facilitate their migration, extravasation and metastatic colonization. Upon exposure of cancer cells to AngII a whole set of genes are regulated, leading to remodeling of the tumor microenvironment. These genes are involved in essential steps of the metastatic progression (extracellular matrix degradation, cell adhesion and migration, uncontrolled cell proliferation, inflammation).
AngII may thus appear as a pro-metastatic microenvironmental signal contributing to the cross-talk between cancer and stromal cells. These findings are of particular importance for the development of personalized therapies against a subset of tumors overexpressing AngII or its receptors. Indeed, agents that block either AngII production or activation are already widely used in the clinics as anti-hypertensive molecules with mild side effects.
From Rodrigues-Ferreira et al., PlosOne 7(4):e35667 (2012)
- Rodrigues-Ferreira S, Abdelkarim M, Dillenburg-Pilla P, Luissint AC, di-Tommaso A, Deshayes F, Pontes CL, Molina A, Cagnard N, Letourneur F, Morel M, Reis RI, Casarini DE, Terris B, Couraud PO, Costa-Neto CM, Di Benedetto M, Nahmias C. Angiotensin II facilitates breast cancer cell migration and metastasis. PLoS One. 7(4):e35667 (2012).
- Rodrigues-Ferreira S, Morel M, Reis RI, Cormier F, Baud V, Costa-Neto CM, Nahmias C. A Novel Cellular Model to Study Angiotensin II AT2 Receptor Function in Breast Cancer Cells. Int J Pept. 2012:745027 (2012).