Role of the Renin-Angiotensin System in Gynecologic Cancers

K.      Ino; K.      Shibata; E.      Yamamoto; H.      Kajiyama; A.      Nawa; Y.      Mabuchi; S.      Yagi; S.      Minami; Y.      Tanizaki; A.      Kobayashi; F.      Kikkawa

Abstract

Recent studies have shown an activation of the local renin-angiotensin system (RAS) in various tumor tissues, including the abundant generation of angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) and the upregulation of angiotensin II type 1 receptor (AT1R) expression. Thus, considerable attention has been paid not only to the role of the RAS in cancer progression, but also to the blockade of RAS as a new approach to the treatment of human cancer. There is increasing evidence that the Ang II-AT1R pathway is involved in tumor growth, angiogenesis and metastasis in various experimental animal models, suggesting the therapeutic potential of an ACE inhibitor and AT1R blocker. In addition, specific Ang II-degrading enzymes are also expressed in tumors and play a regulatory role in tumor cell proliferation and invasion. This review focuses on the role of the RAS in the progression of gynecologic cancers, such as cervical cancer, endometrial cancer, ovarian cancer, and gestational choriocarcinoma. We present here the clinical potential of blocking the RAS as a novel and promising strategy for the treatment of gynecologic cancers.

Keywords: Angiogenesis, Angiotensin II type 1 receptor, Cervical cancer, Endometrial cancer, Ovarian cancer, Reninangiotensin system (RAS), Survival, Vascular endothelial growth factor, Adipocyte-derived leucine aminopeptidase, Aminopeptidase A