Cell of origin affects tumour development and phenotype in pancreatic ductal adenocarcinoma

摘要

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumour thought to arise from ductal cells via pancreatic intraepithelial neoplasia (PanIN) precursor lesions. Modelling of different genetic events in mice suggests both ductal and acinar cells can give rise to PDAC. However, the impact of cellular context alone on tumour development and phenotype is unknown.We examined the contribution of cellular origin to PDAC development by inducing PDAC-associated mutations, KrasG12D expression and LSL-G12D;Trp53flox/floxcKOCreER;KrasLSL-G12D;Trp53flox/floxcKOBoth mouse models developed PDAC, but cKOcKOcKOcKOThese findings indicate that ductal cells are primed to form.