Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival

Abstract

Angiotensin II, a main effector peptide in the renin -angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT 1 R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT 1 R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT 1 R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT 1 R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n ¼ 67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type 1 angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT 1 R, the overall survival and progression-free survival were significantly poor (P ¼ 0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT 1 R, although VEGF, but not AT 1 R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT 1 R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.

Specific single chain variable fragment (ScFv) antibodies to angiotensin II AT2 receptor: evaluation of the angiotensin II receptor expression in normal and tumor-bearing mouse lung

“…Increasing evidence suggests that angiotensin II signaling plays an important role in carcinogenesis (Fujita et al 2005;Ino et al 2006;Kanehira et al 2005;Suganuma et al 2005;Takagi et al 2002:Egami 2003. However, the specific role of AT 2 in carcinogenesis has not been rigorously elucidated.…”

“…4 and 5). Since AT 1 -mediated Ang II signaling has been shown to be associated with the growth of various type of tumors such as melanoma (Egami et al 2003), ovarian cancer, (Ino et al 2006), and lung metastasis of renal cell carcinoma (Miyajima et al 2002), AT 1 over-expression in adenomatous epithelial cells may be associated with cell growth in adenoma. In support of this speculation, AT 1 signaling is shown to stimulate production of vascular endothelial cell growth factor (Fujiyama et al 2001;Richard et al 2000) and stimulate cell growth in multiple cell types (Berry et al 2001;Chung et al 1998).…”

Immunohistochemical Expression of Glut-1 in Epithelial Ovarian Tumors: Correlation With the Clinicopathological Factors and Tumor Proliferative Marker Pcna.

“…PCNA was considered positive if there was any brown nuclear staining present. To assess proliferation, the PCNA labelling index (PCNA LI), was calculated following the previously described method by Ino et al [6]. The PCNA LI was defined as the number of tumor cells with nuclear PCNA immunostaining divided by the total number of tumor cells, and expressed as a percentage.…”

“…Beside these well-known clinical prognostic factors, the applying and usage of molecular techniques is more accurately related to the intrinsic behavior of the tumors and the pathway of carcinogenesis and may be supportive in improving the prognosis of patients with ovarian carcinomas [6].…”

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

“…The polyclonal antirabbit AT1 receptor antibody (306, catalogue SC579) is specific for AT1 and is mouse, rat, and human reactive; it does not show cross-reactivity with AT2 (Lu et al, 1998;Ino et al, 2003Ino et al, , 2006, and AT-2 (Goat polyclonal IgG Santa Cruz Biotechnology Inc.) was 1 : 300 in BSA 1% in PBS.…”