Abstract 2723: The chorio-allantoicmembrane (CAM) model for testing HOX gene antagonism in pancreatic cancer.

Abstract

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid cancers with a 5-year survival rate approaching a dismal 5%. New therapeutic targets need to be identified in order to increase survival rates. HOX genes are a family of 39 transcription factors involved in embryonic development and which have been found to be dys-regulated in PDAC. HOX gene function can be antagonised by HXR9, a peptide that competitively inhibits binding of HOX proteins to their co-factor PBX. We established that the CAM model recapitulates human PDAC, including desmoplasia, and is highly suitable for the evaluation of HXR9 in vivo. Experimental procedure Four PDAC-derived cell lines (AsPc-1, BxPc-3, PaCa-3 and PancTu1) were treated in vitro with HXR9. Ic50s were determined using both MTS and LDH assays. FACS analysis was used to determine mechanisms of cell death. Cell lines were subsequently implanted in the CAM using Marigel™ on embryonic day (EDD) 10. Tumour growth curves were established and tumours were resected and subsequently stained with PDAC-specific cell surface markers. CAM-tumours were treated with intra-tumoral injection of HXR9 on EDD 16. Results PDAC-derived cell lines were sensitive to HXR9 in vitro with IC50s ranging from 13-45μM. Annexin V-PE analysis showed apoptosis was induced in HXR9 treated cells. PDAC was established in the CAM from cell lines and showed remarkable similarity to human disease including desmoplasia and phonotypic markers. Intra-tumoral treatment of CAM-PDAC showed evidence of tumour regression and apoptosis. Conclusions The CAM model is a simple and robust assay for modelling human PDAC and recapitulates architecture including desmoplasia. The CAM assay is suitable for testing the efficacy of HXR9. Targeting HOX gene dys-regulation is a novel approach for the treatment of PDAC. Citation Format: Sophie Gray, Stephen Metcalf, Angela Boxall, Gary Middleton, Izhar Bagwan, Hardev Pandha, Richard Morgan. The chorio-allantoicmembrane (CAM) model for testing HOX gene antagonism in pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2723. doi:10.1158/1538-7445.AM2013-2723