Doublecortin-like kinase 1 is elevated serologically in pancreatic ductal adenocarcinoma and widely expressed on circulating tumor cells

PLoS One. 2015 Feb 27;10(2):e0118933. doi: 10.1371/journal.pone.0118933. eCollection 2015.

Abstract

Doublecortin-like kinase 1 (DCLK1) is a putative pancreatic stem cell marker and is upregulated in pancreatic cancer, colorectal cancer, and many other solid tumors. It marks tumor stem cells in mouse models of intestinal neoplasia. Here we sought to determine whether DCLK1 protein can be detected in the bloodstream and if its levels in archived serum samples could be quantitatively assessed in pancreatic cancer patients. DCLK1 specific ELISA, western blotting, and immunohistochemical analyses were used to determine expression levels in the serum and staining intensity in archived tumor tissues of pancreatic ductal adenocarcinoma (PDAC) patients and in pancreatic cancer mouse models. DCLK1 levels in the serum were elevated in early stages of PDAC (stages I and II) compared to healthy volunteers (normal controls). No differences were observed between stages III/IV and normal controls. In resected surgical tissues, DCLK1 expression intensity in the stromal cells was significantly higher than that observed in tumor epithelial cells. Circulating tumor cells were isolated from KPCY mice and approximately 52% of these cells were positive for Dclk1 staining. Dclk1 levels in the serum of KPC mice were also elevated. We have previously demonstrated that DCLK1 plays a potential role in regulating epithelial mesenchymal transition (EMT). Given the increasingly recognized role of EMT derived stem cells in cancer progression and metastasis, we hypothesize that DCLK1 may contribute to the metastatic process. Taken together, our results suggest that DCLK1 serum levels and DCLK1 positive circulating tumor cells should be further assessed for their potential diagnostic and prognostic significance.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Animals
  • CA-19-9 Antigen / blood
  • Carcinoma, Pancreatic Ductal / blood*
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Case-Control Studies
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Gene Expression
  • Humans
  • Intracellular Signaling Peptides and Proteins / blood*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Protein-Serine-Threonine Kinases / blood*
  • Protein-Serine-Threonine Kinases / genetics*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology

Substances

  • CA-19-9 Antigen
  • Intracellular Signaling Peptides and Proteins
  • DCLK1 protein, human
  • Protein-Serine-Threonine Kinases