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

BACKGROUND: Although agonistic autoantibodies against type-1 angiotensin-II receptor (AT(1)-AA) are frequently detected in women with preeclampsia, the clinical significance of AT(1)-AA in association with epithelial ovarian cancer (EOC) has not been identified. METHODS: In an attempt to clarify this issue, we measured serum AT(1)-AA titer from EOC patients (n = 89) and healthy normal subjects (n = 55), correlated AT(1)-AA titer with EOC stage and grade, and demonstrated the effects of purified AT(1)-AA on migration of ovarian cancer cells and angiogenesis of chick embryo chorioallantoic membrane. RESULTS: We found that the AT(1)-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 AT(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 < 0.01). Furthermore, AT(1)-AA directly stimulated migration of ovarian cancer cells and enhanced microvascular density of chick embryo chorioallantoic membrane. These AT(1)-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 AT(1)-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 AT(1)-AA might be selected as a detectable biomarker and potential therapeutic target in diagnosis and treatment of EOC patients.