Ductal vs. acinar? Recent insights into identifying cell lineage of pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival rate of less than 8%. To date, there are no early detection methods or effective treatments available. Many questions remain to be answered in regards to the pathogenesis of PDAC, among which, the controversy over the cell lineage of PDAC demands more attention. Ductal cells were originally thought to be the cell of origin for PDAC due to the ductal morphology of most cases of PDAC. However, recent studies have demonstrated that acinar cells are more sensitive to KRAS mutation and tend to develop to PanIN and PDAC effectively, very likely by undergoing acinar to ductal metaplasia into a transient state that contributes to PDAC initiation. There is also evidence that both ductal and acinar cells can potentially develop to PDAC when exposed to certain genetic settings and stimuli, suggesting that more scrutiny is required for the identification of the true cell lineage of individual cases of PDAC. In this work, we summarize recent findings in the identification of the cellular origin of PDAC, with the goal of advancing our knowledge on the initiation and progression of the disease. We also discuss various models and techniques for investigating early events of PDAC. Better understanding of these cellular events is crucial to identify new methods for the early diagnosis and treatment of PDAC.

The clinical significance of apolipoprotein L1 in head and neck squamous cell carcinoma

“…Similarly, OSCC and LSCC are also derived from squamous epithelial cells, therefore the expression of APOL1 in cancer may be dependent on the cell type. However, the dominant histological type of PC was pancreatic ductal adenocarcinoma, derived from ductal or acinar cells, and RCC originates in proximal renal tubular epithelial cells ( 65 , 66 ).…”

Nuclear GSK-3β and Oncogenic KRas Promote Expansion of Terminal Duct Cells and the Development of Intraductal Papillary Mucinous Neoplasm

“…Sequencing from human specimens has shown an overlap of somatic mutations between PanIN and IPMN, including the activating mutation of KRas, the most frequent and earliest genetic alteration in PDA (11,12), and the secondary loss-of-function mutation of tumor suppressors TP53 and SMAD4/DPC4, particularly in high-grade lesions (13). Moreover, lineage-tracing experiments and cell-type specific activation of oncogenic KRas coupled to other genetic alterations have been conducted and the collective data demonstrate that, although acinar cells possess the highest plasticity to be transformed and are responsible for most PanIN and IPMN lesions through acinar-to-ductal metaplasia (ADM), ductal cells harboring oncogenic KRas can also give rise to precursor lesions sharing similar histology features, and might also serve as a cell-of-origin for PDA (9,10,14–16). Thus, delineating the origin of PDA precursor lesions with deeper molecular insight could facilitate the development of clinical tools for early-detection and improve PDA patient outcomes in the clinic.…”

Mercury in Pancreatic Cells of People with and without Pancreatic Cancer

“…The carcinogenic potential of mercury would be enhanced if it were present in progenitor cells since these cells when dividing are likely to be susceptible to the genotoxic properties of mercury [10,11]. However, uncertainty remains as to the location of progenitor cells in the human pancreas, with the possibility that they exist in islets, acini, or ducts, or all three locations [25,[28][29][30][31][32]. Future studies combining elemental biomapping with immunostaining for progenitor and stem cell markers would be required to accurately determine the nature of these mercury-containing pancreatic cells.…”