Abstract 1567: Pancreatic tumor cell secreted Cyr61/CCN1 enhances abnormal angiogenesis: A key event for metastasis

Abstract

Abstract CYR61/CCN1, a member of the cysteine rich 61/connective tissue growth factor/nephroblastoma over expressed (CYR61/CTFG/NOV) family of growth factors, is a pro-angiogenic factor that mediates diverse roles in development, cell proliferation, and tumorigenesis. In our previous studies, we have demonstrated that Cyr61 is highly expressed in aggressive pancreatic cancer cell lines. The objective of this study is to evaluate whether tumor cell-secreted Cyr61 is able to enhance the interactions of endothelial cells and vascular smooth muscle cells for remodeling of vasculature. To do so, we determined the impact of conditioned media (CM) of different pancreatic cancer cell lines and their side populations on in vitro and in vivo angiogenesis. The in vitro angiogenesis assay demonstrates that the CM of Cyr61 positive pancreatic cancer cells drastically altered the angiogenesis. CM induces deformed capillary-like structures as compared to regular media and this effect is cell type specific. Moreover, CM also drastically altered the attachment of vascular smooth muscle cells to the capillaries. These in vitro studies were further confirmed by in vivo gel foam assay in mice. The abnormal effects of CM can be overruled by nullifying the Cyr61 expression through Cyr61-specific shRNA or neutralizing Cyr61 antibody. Collectively, these studies suggest that Cyr61 could be a target molecule to normalize the angiogenesis to prevent metastatic growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1567. doi:10.1158/1538-7445.AM2011-1567