The role of angiotensin II in cancer metastasis: Potential of renin-angiotensin system blockade as a treatment for cancer metastasis

Hypertension, which often exists as a comorbid condition in cancer patients, is considered as a factor affecting cancer progression. The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, and angiotensin II (Ang II) is a well-known pressor peptide in RAS. There is also accumulated evidence indicating that Ang II plays a critical role in the metastasis of various cancers by modulating adhesion, migration invasion, proliferation, and angiogenesis. Consistent with this, large epidemiological studies have reported the potential beneficial effects of angiotensin-converting enzyme (ACE) inhibitors and Ang II type 1 receptor blockers (ARBs) against cancer metastasis; however, some of the results remain controversial. Although the precise Ang II-related mechanisms involved in cancer metastasis are not completely clear yet, a number of basic and meta-analytic studies have shown that ACE inhibitors and ARBs reduce the metastatic potential of tumors. In this review, we summarize the relationships among hypertension, RAS, and metastasis as demonstrated in basic and clinical studies. Finally, we discuss the possibility of using RAS inhibitors as anti-metastatic drugs.