Multiple roles of angiotensin in colorectal cancer

Abstract

Colorectal cancer (CRC) cells express renin and chymase through which they can activate angiotensin. Renin expression is induced by hyperglycemic conditions. As angiotensinogen is produced in the liver, CRC cells that can activate angiotensin have an enhanced ability to metastasize to this organ. In human CRC cases, patients with diabetes have higher activities of rennin and angiotensin-II in primary tumors, and on average, have a more progressed disease stage, especially with respect to liver metastasis. These patients exhibit a stronger association with Hemoglobin A1c levels and metastasis compared to patients without diabetes. In a combined diabetes/CRC liver metastasis mouse model, concurrent treatment with anti-angiotensin and hypoglycemic agents shows a synergic effect in terms of reduced liver metastasis and improved survival. The effect of anti-angiotensin treatment and blood sugar control as a baseline management for colon cancer patients with diabetes needs to be examined in clinical trials to establish whether it can prevent liver metastasis.

Keywords: Angiotensin; Angiotensin II receptor blocker; Diabetes; Liver metastasis; Renin.

Figure 1

Aniotensinogen is activated to become a bioactive form, angiotensin II by some enzymes, such as ACE. In angiotensin receptors (blue boxed), angiotensin II type 1 receptor is pro-tumoral; however, angiotensin II type 2 receptor is not definitive. Angiotensin 1-7, a degraded product of angiotensin IIactivates MAS1 receptor to provide inhibitory effects. Substances marked with yellow boxes are possible inhibitors for angiotensin effects.