Journal
CANCER LETTERS
Volume 423, Issue -, Pages 71-79Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.03.009
Keywords
Pancreatic IPMN; DCLK1; SOX9; KLF4
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Funding
- NIH/NCI [R01 CA217207, R01 CA178445]
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PanINs and IPMNs are the two most common precursor lesions that can progress to invasive pancreatic ductal adenocarcinoma (PDA). DCLK1 has been identified as a biomarker of progenitor cells in PDA progressed from PanINs. To explore the potential role of DCLK1-expressing cells in the genesis of IPMNs, we compared the incidence of DCLK1-positive cells in pancreatic tissue samples from genetically-engineered mouse models (GEMMs) for IPMNs, PanINs, and acinar to ductal metaplasia by immunohistochemistry and immunofluorescence. Mouse lineage tracing experiments in the IPMN GEMM showed that DCLK1(+) cells originated from a cell lineage distinct from PDX1(+) progenitors. The DCLK1 cells shared the features of tuft cells but were devoid of IPMN tumor biomarkers. The DCLK1(+) cells were detected in the earliest proliferative acinar clusters prior to the formation of metaplastic ductal cells, and were enriched in the IPMN niches. In summary, DCLK1 labels a unique pancreatic cellular lineage in the IPMN GEMM. The clustering of DCLK1(+) cells is an early event in Kras-induced pancreatic tumorigenesis and may contribute to IPMN initiation. (C) 2018 Elsevier B.V. All rights reserved.
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