Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas

Am J Physiol Gastrointest Liver Physiol. 2010 Aug;299(2):G303-10. doi: 10.1152/ajpgi.00146.2010. Epub 2010 Jun 3.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Separation / methods
  • Epithelial Cells / cytology
  • Intermediate Filament Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Pancreas / cytology*
  • Pancreas / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spheroids, Cellular / cytology
  • Stem Cells / metabolism*
  • Tissue Distribution

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Neurog3 protein, mouse
  • Dcamkl1 protein, mouse
  • Protein-Serine-Threonine Kinases