Abstract
BackgroundAlthough agonistic autoantibodies against type-1 angiotensin-II receptor (AT1-AA) are frequently detected in women with preeclampsia, the clinical significance of AT1-AA in association with epithelial ovarian cancer (EOC) has not been identified.MethodsIn an attempt to clarify this issue, we measured serum AT1-AA titer from EOC patients (n = 89) and healthy normal subjects (n = 55), correlated AT1-AA titer with EOC stage and grade, and demonstrated the effects of purified AT1-AA on migration of ovarian cancer cells and angiogenesis of chick embryo chorioallantoic membrane.ResultsWe found that the AT1-AA titer was significantly higher in EOC patients compared with healthy control subjects (1.77 ± 0.28 vs. 0.35 ± 0.05, P < 0.01). The positive rate was averaged by 72.1±2.5% in EOC patients and 15.5 ±1.5% in control (P < 0.01). Increased AT1-AA titer in EOC patients was associated with advanced stages and grades of EOC, and positively correlated with level of vascular endothelial growth factor (r = 0.855, P < 0.01). Furthermore, AT1-AA directly stimulated migration of ovarian cancer cells and enhanced microvascular density of chick embryo chorioallantoic membrane. These AT1-AA-mediated effects were significantly blocked either by an autoantibody-neutralizing peptide or an angiotensin II type I receptor antagonist, losartan.ConclusionTaken together, we found that a higher serum AT1-AA titer may be associated with advanced progression of EOC in patients and play an important role in development of EOC by promoting cancer cell migration and angiogenesis. These findings implicate that AT1-AA might be selected as a detectable biomarker and potential therapeutic target in diagnosis and treatment of EOC patients.
Highlights
Agonistic autoantibodies against type-1 angiotensin-Angiotensin II (II) receptor (AT1-AA) are frequently detected in women with preeclampsia, the clinical significance of angiotensin II (Ang II) type 1 (AT1)-AA in association with epithelial ovarian cancer (EOC) has not been identified
Using Agonistic autoantibodies against type-1 angiotensin-II receptor (AT1-AA) purified from EOC patients, we demonstrated the effects of Ang II type 1 (AT1)-AA on migration of ovarian cancer cells and microvascular density of chick embryo chorioallantoic membrane
Our results showed that higher AT1-AA titer is positively correlated with vascular endothelial growth factor (VEGF) level in advanced stages of EOC patients, consistent with previous findings showing a role of Ang II in cancer development through VEGF gene expression and secretion [8,17]
Summary
Agonistic autoantibodies against type-1 angiotensin-II receptor (AT1-AA) are frequently detected in women with preeclampsia, the clinical significance of AT1-AA in association with epithelial ovarian cancer (EOC) has not been identified. Epithelial ovarian cancer (EOC) is the sixth most common cancer and the seventh cause of death worldwide among women who develop gynecological cancer [1], with the estimated 22,280 new cases and 15,500 deaths in the United States in 2012. In patient with EOC, it has previously been reported that Ang II enhances vascular endothelial growth factor (VEGF) secretion, angiogenesis and tumor cell invasion via up-regulating G-protein-coupled AT1 receptor; importantly, angiogenesis and peritoneal dissemination of the EOC can selectively be blocked using AT1 receptor antagonist [6,8]. Considerable effort has been placed on the development of Ang II blockade therapy as a new strategy for EOC treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
