Doublecortin-like kinase 1 is elevated serologically in pancreatic ductal adenocarcinoma and widely expressed on circulating tumor cells.
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.
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, OK, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, United States of America.
Dongfeng
D
Qu
Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Jeremy
J
Johnson
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, United States of America.
Parthasarathy
P
Chandrakesan
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Nathaniel
N
Weygant
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, OK, United States of America.
Randal
R
May
Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Nicole
N
Aiello
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America.
Andrew
A
Rhim
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Lichao
L
Zhao
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Wei
W
Zheng
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Stanley
S
Lightfoot
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Shubham
S
Pant
Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Jeremy
J
Irvan
Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Russell
R
Postier
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
James
J
Hocker
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Jay S
JS
Hanas
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, United States of America.
Naushad
N
Ali
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, OK, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, United States of America.
Sripathi M
SM
Sureban
Department of Oncology, Beijing Chaoyang Hospital, Capital Medicinal University, Beijing, China.
Guangyu
G
An
COARE Biotechnology Inc., Oklahoma City, OK, United States of America.
Michael J
MJ
Schlosser
Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Ben
B
Stanger
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, OK, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, United States of America; COARE Biotechnology Inc., Oklahoma City, OK, United States of America.
Courtney W
CW
Houchen
D000328:Adult; D000368:Aged; D000818:Animals; D018395:CA-19-9 Antigen / Q000097:blood; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D000089742:Doublecortin-Like Kinases; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000097:blood* / Q000235:genetics*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D018395:CA-19-9 Antigen; D047908:Intracellular Signaling Peptides and Proteins; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases