Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas.
Stem cells are critical in maintaining adult homeostasis and have been proposed to be the origin of many solid tumors, including pancreatic cancer. Here we demonstrate the expression patterns of the putative intestinal stem cell marker DCAMKL-1 in the pancreas of uninjured C57BL/6 mice compared with other pancreatic stem/progenitor cell markers. We then determined the viability of isolated pancreatic stem/progenitor cells in isotransplantation assays following DCAMKL-1 antibody-based cell sorting. Sorted cells were grown in suspension culture and injected into the flanks of athymic nude mice. Here we report that DCAMKL-1 is expressed in the main pancreatic duct epithelia and islets, but not within acinar cells. Coexpression was observed with somatostatin, NGN3, and nestin, but not glucagon or insulin. Isolated DCAMKL-1+ cells formed spheroids in suspension culture and induced nodule formation in isotransplantation assays. Analysis of nodules demonstrated markers of early pancreatic development (PDX-1), glandular epithelium (cytokeratin-14 and Ep-CAM), and isletlike structures (somatostatin and secretin). These data taken together suggest that DCAMKL-1 is a novel putative stem/progenitor marker, can be used to isolate normal pancreatic stem/progenitors, and potentially regenerates pancreatic tissues. This may represent a novel tool for regenerative medicine and a target for anti-stem cell-based therapeutics in pancreatic cancer.
Dept. of Medicine, Univ. of Oklahoma Health Sciences Center, Oklahoma City, 73104, USA.
Randal
R
May
Sripathi M
SM
Sureban
Stan A
SA
Lightfoot
Aimee B
AB
Hoskins
Daniel J
DJ
Brackett
Russell G
RG
Postier
Rama
R
Ramanujam
Chinthalapally V
CV
Rao
James H
JH
Wyche
Shrikant
S
Anant
Courtney W
CW
Houchen
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods; D000089742:Doublecortin-Like Kinases; D004847:Epithelial Cells / Q000166:cytology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology; D013234:Stem Cells / Q000378:metabolism*; D014018:Tissue Distribution
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D000089742:Doublecortin-Like Kinases; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D017346:Protein Serine-Threonine Kinases; C577485:Nes protein, mouse; C407737:Neurog3 protein, mouse; C485525:Dclk1 protein, mouse