Hypoxia-induced angiotensin II by the lactate-chymase-dependent mechanism mediates radioresistance of hypoxic tumor cells.

ABSTRACT: The renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism. We further demonstrate in nasopharyngeal carcinoma CNE2 and 5-8F cells that this chymase-dependent effect is mediated by increased levels of lactate, a by-pr

SUBMITTER: Xie G 

PROVIDER: S-EPMC5311966 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature