Abstract 1846: Cyr61 a therapeutic target for breast carcinomas

Abstract

Abstract Background: Cyr61, also known as CCN1, is a survival and pro-angiogenic factor overexpressed in invasive breast tumors that promotes tumorigenicity. We investigated whether Cyr61 plays important roles in breast cancer and evaluated its potential role as a chemotherapeutical target. Methods: We analyzed Cyr61 expression in a tissue microarray from breast cancer patients consisting of primary breast carcinomas and recurrences. Cyr61 was silenced in the metastatic MDA-MB-231 cells using a Cyr61-specific short hairpin RNA (Cyr61-shRNA). The effect of Cyr61 silencing on anchorage dependent- and independent growth, migration and invasiveness was characterized in vitro. The mechanism by which Cyr61 mediates the proliferation effects was investigated. The effect of Cyr61 in tumor growth was investigated in a subcutaneous orthotopic tumor xenograft model and the histological and immunohistochemical analysis ware performed. All statistical tests were two-sided. Results: Cyr61 is highly expressed in about 47% of the metastatic breast cancer patients analyzed. The expression is higher in the recurrences than in the primary tumors. Silencing Cyr61 inhibits cell proliferation, prevents anchorage-dependent and -independent growth, and suppresses the invasive potential of the cells by inhibiting migration in vitro. We also found that silencing Cyr61 decreases the expression of its own receptor αvβ3, and decreases its signaling activities. Remarkably, the in vivo studies showed that after silencing Cyr61 the tumor burden is significantly decreased and there is poor vascularized compared to control tumors. Conclusions: Our findings provide the proof of concept that Cyr61 is a key promoter of breast cancer tumorigenicity. It should be considered as a potential target for developing therapies to breast cancers patients that overexpress Cyr61. 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 1846. doi:1538-7445.AM2012-1846