PO-131 Over expression of extracellular matrix protein 1 (ECM1) in muscle-invasive bladder cancer

Introduction Bladder cancer (BC) is the ninth most common cancer worldwide. A quarter of all cases present as muscle invasive BC (MIBC). Treatment for this group has remained largely unchanged for the past 20 years limited mainly to cisplatin based therapy and radical cystectomy. Prognosis for these patients is poor, with 5 year survival Material and methods ECM1 expression was assessed at the mRNA and protein levels in 47 bladder tumour derived cell lines using qRT-PCR and western blot analysis. ECM1 knockdown cell lines were established using shRNA lentiviral transduction in a panel of cell lines which overexpress the protein. ECM1 knockdown cell lines were analysed for phenotypic effects. Phosphorylation of EGFR and downstream effectors was examined following recombinant ECM1 treatment. Publicly available microarray data was mined to assess the clinical significance of ECM1 expression in patients, relating high expression to tumour stage and overall survival. Results and discussions ECM1 knockdown had an inhibitory effect on wound-healing ability. Evidence suggests ECM1 initiates phosphorylation and thus activation of EGFR and downstream effectors in the pathway, however we have been unable to detect a direct interaction with EGFR as described in breast. Mining of publicly available data revealed a significant association between high ECM1 expression and reduced overall survival. Conclusion ECM1 overexpression in MIBC appears to be associated with poorer prognosis in patients. While ECM1 has been shown to influence EGFR signalling, the mechanism of EGFR activation by ECM1 in BC may be different from that previously described in breast cancer.