Role of the Renin-Angiotensin System in Gynecologic Cancers

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.

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…Angiogenesis and Cancer. AT 1 receptor-regulated cell proliferation and angiogenesis has biologic and therapeutic implications in cancer (Escobar et al, 2004;Deshayes and Nahmias, 2005;Uemura et al, 2005Uemura et al, , 2006Uemura et al, , 2011Ino et al, 2011;Lau and Leung, 2011;Uemura and Kubota, 2012). Local AngII production is a proangiogenic stimulus in tumor microenvironment.…”

GPCRs and cancer

“…Recently, Ang-II exhibited in vitro and in vivo the potential to enhance the expression of AR in prostate cancer cells through angiotensin II type-1 receptor (AT1R) [106] . In addition, Ang-II and BK receptors have been implicated in the development, growth, angiogenesis and metastasis in a wide number of tumors [101,102,[107][108][109][110][111] . For instance, Ang-II and BK stimulated DNA synthesis in pancreatic cancer cells [112] .…”

Association of angiotensin ІІ type 1 receptor (A1166C) polymorphism with breast cancer risk: An update meta-analysis

“…31,32 Recently, a SNPs A1166C polymorphism was reported to be associated with the risk for breast cancer. 15,21,22 However, the results were inconsistent between each study.…”