Abstract 1485: The role of angiopoietin family members in the progression of ovarian cancer

Despite advances in surgical debulking, radiation, and chemotherapy over the past few decades, ovarian carcinoma remains the most deadly gynecological malignancy. This is largely due to the lack of early stage detection manifesting in approximately 80% of patients presenting with metastatic disease at the time of diagnosis. Current chemotherapeutic drugs are effective only for a short period as patients with advance disease eventually develop resistance despite significant initial responses. Thus, there is a pressing need for the identification of novel therapeutic targets in ovarian cancer. Mounting evidence suggests that the Angiopoietin/Tie-2 functional axis has wide-ranging effects on tumor angiogenesis and progression of a variety of cancer types, however, the expression profiles and biological effects of the Angiopoietin family members on ovarian cancer remain largely unknown. Our data show for the first time that Ang-1, Ang-2 and Ang-4 are expressed in ovarian cancer cell lines and patient samples from both primary and secondary tumor lesions. More specifically, patient tumors revealed a unique localization pattern of Angiopoietin family members whereby Ang-1 and Ang-2 are robustly expressed in tumor cells and stroma, whereas Ang-4 expression is predominately in the tumor stroma. In addition, we show that overexpression of Ang-4 and Ang-2 and, to a lesser extent, Ang-1, promotes subcutaneous growth of ovarian cancer cells and results in accelerated ascites formation and poor survival in an orthotopic ovarian cancer mouse model. Immunohistochemical analysis of orthotopic tumors suggests the pro-growth effects of Ang-1 and Ang-4 are mediated through increased tumor cell proliferation as determined by positive Ki67 staining. Our results also demonstrated that ovarian cancer cells express Tie-2 receptor tyrosine kinase (RTK), the angiopoietin receptor. The expression of Tie-2, as well as angiopoietin family members, by ovarian cancer cells suggests the potential of an Angiopoietin/Tie-2 autocrine loop. Lastly, further analysis suggests the potential role of angiopoietins in increasing the amount of cancer associated fibroblasts (CAFs) in the tumor microenvironment. Taken together, our data suggest that the Angiopoietin/Tie-2 functional axis is a significant player in ovarian cancer progression and is a potential target for ovarian cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1485. doi:1538-7445.AM2012-1485