Gut Liver.  2014 Sep;8(5):508-518. 10.5009/gnl13237.

Cyclooxygenase 2 in Gastric Carcinoma Is Expressed in Doublecortin- and CaM Kinase-Like-1-Positive Tuft Cells

• Mutoh H
• Sashikawa
• Sakamoto H
• Tateno T

• KMID: 2070061
• DOI: http://doi.org/10.5009/gnl13237

Abstract

BACKGROUND/AIMS
Doublecortin and CaM kinase-like-1 (DCAMKL1) is a marker of stem cells expressed predominantly in the crypt base in the intestine. However, DCAMKL1-positive cells have been shown to be differentiated tuft cells rather than quiescent progenitors. Tuft cells are the only epithelial cells that express cyclooxygenase 2 (COX-2) in the normal intestinal epithelium. We previously generated Cdx2-transgenic mice as model mice for intestinal metaplasia and gastric carcinoma. In the current study, we investigated the association between COX-2 and DCAMKL1 in gastric carcinoma.
METHODS
We examined the association between COX-2 and DCAMKL1 expression in gastric carcinomas in clinical samples (early gastric well-differentiated adenocarcinoma) and Cdx2-transgenic mice; and the DCAMKL1-transgenic mouse stomach using immunohistochemistry and quantitative real-time polymerase chain reaction.
RESULTS
The COX-2-expressing cells were scattered, not diffusely expressed, in gastric carcinomas from humans and Cdx2-transgenic mice. DCAMKL1-positive cells were also scattered in the gastric carcinomas, indicating that tuft cells could still be present in gastric carcinoma. COX-2 was expressed in DCAMKL1-positive tuft cells in Cdx2- and DCAMKL1-transgenic mouse stomachs, whereas the Sox9 transcription factor was ubiquitously expressed in gastric carcinomas, including COX-2-positive cells.
CONCLUSIONS
COX-2 is expressed in DCAMKL1-expressing quiescent tuft cells in gastric carcinoma.

Keyword

Sox9; Cdx2-transgenic mice; Stem cell marker

MeSH Terms

Adenocarcinoma/metabolism
Animals
Cyclooxygenase 2/genetics/*metabolism
Epithelial Cells/metabolism
Gastric Mucosa/metabolism
Humans
Intestinal Mucosa/cytology/*enzymology/metabolism
Intracellular Signaling Peptides and Proteins/genetics/*metabolism
Mice
Mice, Transgenic
Protein-Serine-Threonine Kinases/genetics/*metabolism
SOX9 Transcription Factor/genetics/metabolism
Stomach Neoplasms/*enzymology/genetics
Cyclooxygenase 2
Intracellular Signaling Peptides and Proteins
Protein-Serine-Threonine Kinases
SOX9 Transcription Factor