Serum agonistic autoantibodies against type-1 angiotensin II receptor titer in patients with epithelial ovarian cancer: a potential role in tumor cell migration and angiogenesis

摘要

Background Although 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. Methods In 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. Results We 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 1-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 1-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. Conclusion Taken 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.