Protumoral Effect of Angiotensin System.

Abstract

Colorectal cancer (CRC) cells possess an angiotensin activation mechanism provided by the expression of renin and chymase. Renin expression is induced by a hyperglycemic condition. Since angiotensinogen is produced in the liver, CRC cells with angiotensin-activating machinery possess an advantage to metastasize to the liver. In human CRC cases, the diabetes-complicated patients show higher concentrations of renin and angiotensin-Ⅱ in the primary tumors, and a more progressed disease stage, especially, liver metastasis in association with HbA1c levels than those in the patients without diabetes. Concurrent treatment with anti-angiotensin and hypoglycemic agents shows a synergic effect of decreasing liver metastasis and improving the survival of diabetic mice in the CRC liver metastasis model. MAS1-angiotensin1-7 is a negative regulator of the AGTR1-angiotensin Ⅱ axis in breast cancer. Notably, MAS1 is overexpressed in triple negative breast cancer, which might be a novel molecular target for the treatment-refractory entity of breast cancer. Nuclear AGTR2 and intracellular angiotensin-Ⅱ play a role in anti-apoptotic and anti-oxidative stress properties. These functions of nuclear AGTR2 might mitigate "anti-tumoral side effects" of AGTR1 and angiotensin-Ⅱ system, which enhance mainly tumor progression. The effect of anti-angiotensin treatment such as ARB and blood sugar control as ab aseline management of many cancer patients needs to be examined in a clinical situation for prevention of RAS-induced tumor progression.