Acinar cell plasticity and development of pancreatic ductal adenocarcinoma

Pancreatic acinar cells show high plasticity and can undergo acinar-to-ductal metaplasia, which might be an initiating event for pancreatic cancer. Here, the determinants of acinar cell plasticity are discussed, as well as signalling events that drive acinar-to-ductal metaplasia and their contribution to oncogenesis. Acinar cells in the adult pancreas show high plasticity and can undergo transdifferentiation to a progenitor-like cell type with ductal characteristics. This process, termed acinar-to-ductal metaplasia (ADM), is an important feature facilitating pancreas regeneration after injury. Data from animal models show that cells that undergo ADM in response to oncogenic signalling are precursors for pancreatic intraepithelial neoplasia lesions, which can further progress to pancreatic ductal adenocarcinoma (PDAC). As human pancreatic adenocarcinoma is often diagnosed at a stage of metastatic disease, understanding the processes that lead to its initiation is important for the discovery of markers for early detection, as well as options that enable an early intervention. Here, the critical determinants of acinar cell plasticity are discussed, in addition to the intracellular and extracellular signalling events that drive acinar cell metaplasia and their contribution to development of PDAC.