Pancreatic ductal adenocarcinoma and acinar cells: a matter of differentiation and development?

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has long been considered to arise from pancreatic ducts on the basis of its morphology, the occurrence of dysplasia in putative preneoplastic ductal lesions, and the absence of acinar dysplasia in the pancreas of patients with PDAC. However, evidence gathered through both in vitro studies and--more importantly--genetic mouse models of PDAC shows that ductal-type tumours can arise from acinar cells. These findings raise new important questions related to PDAC pathophysiology and call for in-depth studies of acinar cell differentiation in order to better understand PDAC biology. The authors review these issues and discuss how the novel findings should impact on future work aiming at early diagnosis and improved outcome of patients with PDAC.

Sirtuin-1 Regulates Acinar-to-Ductal Metaplasia and Supports Cancer Cell Viability in Pancreatic Cancer

“…In the presence of LMB, when more nuclear Sirt1 is retained, we observed a lesser induction of Krt19, a prominent hallmark of ADM (2,15). This indicated inhibition of ADM to a certain extent.…”

“…There is compelling evidence from mouse models that ADM is a precursor lesion of PDAC (2,3). ADM also occurs in pancreatitis, which may explain why pancreatitis is a major risk factor for PDAC (2,3). Prevention of ADM and maintenance of acinar cell differentiation could suppress pancreatic carcinogenesis.…”

“…New insights in PDAC initiation show that adult exocrine acinar cells under stress can dedifferentiate and gain metaplastic ductal characteristics (referred to as acinar-to-ductal metaplasia, ADM). There is compelling evidence from mouse models that ADM is a precursor lesion of PDAC (2,3). ADM also occurs in pancreatitis, which may explain why pancreatitis is a major risk factor for PDAC (2,3).…”

Role of fibroblast growth factors in pancreatic cancer

“…Наиболее распространена инвазивная протоковая аденокарцинома поджелудочной железы (PDAC), которая диагностируется более чем в 80% опухолей поджелудочной железы [2]. Происхождение PDAC до сих пор окончательно не определено, хотя наиболее вероятным источником считаются метапластические ацинарные клетки, возникшие в результате ацинарно-протоковой трансформации на фоне хронического воспалительного процесса [3]. В подавляющем числе случаев PDAC находят активирующие мутации в онкогене KRAS и инактивирующие мутации в генах опухолевых супрессоров TP53, SMAD4 и CDKN2A [4].…”

Pancreatic carcinoma development: new etiological and pathogenetic evidence

“…The sequence of steps, starting from pre-neoplastic lesions and leading to invasive malignancy, might follow a different course. [51][52][53][54] It has to be emphasized that neither the cells from which pancreatic carcinoma originates, nor its histogenesis, are completely understood, and no univocal conclusions have yet been obtained. Early research reported that this cancer arises from cells of epithelial duct.…”