PO-500 A novel role for junctional adhesion molecule-a (JAM-A) in HER2-positive gastro-oesophageal cancers

Abstract

IntroductionJunctional Adhesion Molecule-A (JAM-A) is a cell-cell adhesion protein that regulates physiological adhesion in epithelial and endothelial cells. Our previous work has shown that increased JAM-A expression on breast tumour epithelial tissue associates with poor prognosis in patients with invasive breast cancer, and identified a correlation between high JAM-A expression and levels of the important oncogene human epidermal growth factor receptor-2 (HER2). An important role for HER2 in gastro-oesophageal cancer is emerging, however the specific role of JAM-A in this setting is unclear.Material and methodsIn a pilot study, gastric cancer patient tissue sections (n=11) were stained for JAM-A expression. A novel, weighted ranking system was developed to semi-quantitatively score the extremely heterogeneous JAM-A membranous staining in gastric tissues; ultimately ranking tissues as low, moderate or high JAM-A expression. JAM-A scores were also correlated with HER2 status in each section. In parallel, a panel of gastro-oesophageal cell lines was used to investigate potential molecular relationships between JAM-A and HER2. Finally, HER2 protein expression was examined following transient JAM-A gene silencing in the gastro-oesophageal junction cancer cell line ESO26.Results and discussionsThe pilot study revealed that high JAM-A expression significantly correlated with HER2 positivity, and noted a novel staining pattern for JAM-A in diffuse gastric cancers. Molecular studies showed that JAM-A gene silencing reduced HER2 protein expression in gastric cancer cells. These data suggests that JAM-A may act as a novel upstream regulator of HER2 in gastro-oesophageal cancer cells, and warrant further investigation. Current studies are focussed on elucidating the mechanisms underpinning regulation of HER2 expression by JAM-A.ConclusionPromising preliminary indications that JAM-A plays a role in regulating HER2 expression in non-breast cancers may suggest it as both an unfavourable biomarker, as well as a novel putative pharmacological target for HER2-positive gastro-oesophageal cancers.This abstract has emanated from research conducted with the financial support of Science Foundation Ireland (SFI) under grant number 13/IA/1994 (to AMH).