Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett's esophagus and esophageal adenocarcinoma

Kenneth J Vega, Randal May, Sripathi M. Sureban, Stan A. Lightfoot, Dongfeng Qu, Alessandra Reed, Nathaniel Weygant, Rama Ramanujam, Rhonda Souza, Mohammad Madhoun, Joshua Whorton, Shrikant Anant, Stephen J. Meltzer, Courtney W. Houchen

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background and Aim: In Barrett's esophagus (BE), the normal esophageal squamous epithelium is replaced with a specialized metaplastic columnar epithelium. BE is a premalignant lesion that can progress to esophageal adenocarcinoma (EAC). Currently, there are no early molecular indicators that would predict progression from BE to EAC. As the only permanent residents of the epithelium, stem cells have been implicated in this metaplastic progression. The aim of the present study was to determine the expression of doublecortin and CaM kinase-like-1 (DCAMKL-1) and other putative gastrointestinal stem cell markers in normal esophageal mucosa (NEM), BE, and EAC. Methods: Human NEM, BE, EAC, and multitissue microarrays were analyzed for DCAMKL-1, and immunohistochemically scored based on staining intensity and tissue involvement, with epithelia and stroma scored separately. Total RNA isolated from BE and paired NEM was subjected to real-time reverse-transcription-polymerase chain reaction analysis for DCAMKL-1, leucine-rich repeat-containing G-protein-coupled receptor (LGR5), and Musashi-1 (Msi-1) mRNA expression. Results: DCAMKL-1 was minimally expressed in squamous NEM, but increased in BE (with and without dysplasia) and EAC tissues. In EAC, we found increased stromal DCAMKL-1 staining compared to adjacent epithelia. Within the submucosa of dysplastic BE tissues, an increase in the endothelial cell expression of DCAMKL-1 was observed. Finally, an upregulation of DCAMKL-1, LGR5, and Msi-1 mRNA was seen in BE compared to squamous NEM. Conclusions: In the present study, we report the progressive increase of DCAMKL-1 expression in BE from dysplasia to EAC. Furthermore, there was an increase in putative stem cell markers DCAMKL-1, LGR5, and Msi-1 mRNA. Taken together, these data suggest that the regulation of resident stem cells might play an important role in the progression of BE to EAC.

Original languageEnglish (US)
Pages (from-to)773-780
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume27
Issue number4
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

Barrett Esophagus
Adenocarcinoma
Phosphotransferases
Stem Cells
Epithelium
Messenger RNA
Staining and Labeling
G-Protein-Coupled Receptors
Leucine
Reverse Transcription
Up-Regulation
Endothelial Cells
Esophageal Mucosa
RNA

Keywords

  • Barrett's esophagus
  • Cancer
  • Doublecortin and CaM kinase-like-1
  • Esophageal adenocarcinoma
  • Esophagus
  • Leucine-rich repeat-containing G-protein-coupled receptor
  • Musashi-1
  • Stem cell marker

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett's esophagus and esophageal adenocarcinoma. / Vega, Kenneth J; May, Randal; Sureban, Sripathi M.; Lightfoot, Stan A.; Qu, Dongfeng; Reed, Alessandra; Weygant, Nathaniel; Ramanujam, Rama; Souza, Rhonda; Madhoun, Mohammad; Whorton, Joshua; Anant, Shrikant; Meltzer, Stephen J.; Houchen, Courtney W.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 27, No. 4, 01.01.2012, p. 773-780.

Research output: Contribution to journalArticle

Vega, KJ, May, R, Sureban, SM, Lightfoot, SA, Qu, D, Reed, A, Weygant, N, Ramanujam, R, Souza, R, Madhoun, M, Whorton, J, Anant, S, Meltzer, SJ & Houchen, CW 2012, 'Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett's esophagus and esophageal adenocarcinoma', Journal of Gastroenterology and Hepatology (Australia), vol. 27, no. 4, pp. 773-780. https://doi.org/10.1111/j.1440-1746.2011.06928.x
Vega, Kenneth J ; May, Randal ; Sureban, Sripathi M. ; Lightfoot, Stan A. ; Qu, Dongfeng ; Reed, Alessandra ; Weygant, Nathaniel ; Ramanujam, Rama ; Souza, Rhonda ; Madhoun, Mohammad ; Whorton, Joshua ; Anant, Shrikant ; Meltzer, Stephen J. ; Houchen, Courtney W. / Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett's esophagus and esophageal adenocarcinoma. In: Journal of Gastroenterology and Hepatology (Australia). 2012 ; Vol. 27, No. 4. pp. 773-780.
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abstract = "Background and Aim: In Barrett's esophagus (BE), the normal esophageal squamous epithelium is replaced with a specialized metaplastic columnar epithelium. BE is a premalignant lesion that can progress to esophageal adenocarcinoma (EAC). Currently, there are no early molecular indicators that would predict progression from BE to EAC. As the only permanent residents of the epithelium, stem cells have been implicated in this metaplastic progression. The aim of the present study was to determine the expression of doublecortin and CaM kinase-like-1 (DCAMKL-1) and other putative gastrointestinal stem cell markers in normal esophageal mucosa (NEM), BE, and EAC. Methods: Human NEM, BE, EAC, and multitissue microarrays were analyzed for DCAMKL-1, and immunohistochemically scored based on staining intensity and tissue involvement, with epithelia and stroma scored separately. Total RNA isolated from BE and paired NEM was subjected to real-time reverse-transcription-polymerase chain reaction analysis for DCAMKL-1, leucine-rich repeat-containing G-protein-coupled receptor (LGR5), and Musashi-1 (Msi-1) mRNA expression. Results: DCAMKL-1 was minimally expressed in squamous NEM, but increased in BE (with and without dysplasia) and EAC tissues. In EAC, we found increased stromal DCAMKL-1 staining compared to adjacent epithelia. Within the submucosa of dysplastic BE tissues, an increase in the endothelial cell expression of DCAMKL-1 was observed. Finally, an upregulation of DCAMKL-1, LGR5, and Msi-1 mRNA was seen in BE compared to squamous NEM. Conclusions: In the present study, we report the progressive increase of DCAMKL-1 expression in BE from dysplasia to EAC. Furthermore, there was an increase in putative stem cell markers DCAMKL-1, LGR5, and Msi-1 mRNA. Taken together, these data suggest that the regulation of resident stem cells might play an important role in the progression of BE to EAC.",
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T1 - Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett's esophagus and esophageal adenocarcinoma

AU - Vega, Kenneth J

AU - May, Randal

AU - Sureban, Sripathi M.

AU - Lightfoot, Stan A.

AU - Qu, Dongfeng

AU - Reed, Alessandra

AU - Weygant, Nathaniel

AU - Ramanujam, Rama

AU - Souza, Rhonda

AU - Madhoun, Mohammad

AU - Whorton, Joshua

AU - Anant, Shrikant

AU - Meltzer, Stephen J.

AU - Houchen, Courtney W.

PY - 2012/1/1

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N2 - Background and Aim: In Barrett's esophagus (BE), the normal esophageal squamous epithelium is replaced with a specialized metaplastic columnar epithelium. BE is a premalignant lesion that can progress to esophageal adenocarcinoma (EAC). Currently, there are no early molecular indicators that would predict progression from BE to EAC. As the only permanent residents of the epithelium, stem cells have been implicated in this metaplastic progression. The aim of the present study was to determine the expression of doublecortin and CaM kinase-like-1 (DCAMKL-1) and other putative gastrointestinal stem cell markers in normal esophageal mucosa (NEM), BE, and EAC. Methods: Human NEM, BE, EAC, and multitissue microarrays were analyzed for DCAMKL-1, and immunohistochemically scored based on staining intensity and tissue involvement, with epithelia and stroma scored separately. Total RNA isolated from BE and paired NEM was subjected to real-time reverse-transcription-polymerase chain reaction analysis for DCAMKL-1, leucine-rich repeat-containing G-protein-coupled receptor (LGR5), and Musashi-1 (Msi-1) mRNA expression. Results: DCAMKL-1 was minimally expressed in squamous NEM, but increased in BE (with and without dysplasia) and EAC tissues. In EAC, we found increased stromal DCAMKL-1 staining compared to adjacent epithelia. Within the submucosa of dysplastic BE tissues, an increase in the endothelial cell expression of DCAMKL-1 was observed. Finally, an upregulation of DCAMKL-1, LGR5, and Msi-1 mRNA was seen in BE compared to squamous NEM. Conclusions: In the present study, we report the progressive increase of DCAMKL-1 expression in BE from dysplasia to EAC. Furthermore, there was an increase in putative stem cell markers DCAMKL-1, LGR5, and Msi-1 mRNA. Taken together, these data suggest that the regulation of resident stem cells might play an important role in the progression of BE to EAC.

AB - Background and Aim: In Barrett's esophagus (BE), the normal esophageal squamous epithelium is replaced with a specialized metaplastic columnar epithelium. BE is a premalignant lesion that can progress to esophageal adenocarcinoma (EAC). Currently, there are no early molecular indicators that would predict progression from BE to EAC. As the only permanent residents of the epithelium, stem cells have been implicated in this metaplastic progression. The aim of the present study was to determine the expression of doublecortin and CaM kinase-like-1 (DCAMKL-1) and other putative gastrointestinal stem cell markers in normal esophageal mucosa (NEM), BE, and EAC. Methods: Human NEM, BE, EAC, and multitissue microarrays were analyzed for DCAMKL-1, and immunohistochemically scored based on staining intensity and tissue involvement, with epithelia and stroma scored separately. Total RNA isolated from BE and paired NEM was subjected to real-time reverse-transcription-polymerase chain reaction analysis for DCAMKL-1, leucine-rich repeat-containing G-protein-coupled receptor (LGR5), and Musashi-1 (Msi-1) mRNA expression. Results: DCAMKL-1 was minimally expressed in squamous NEM, but increased in BE (with and without dysplasia) and EAC tissues. In EAC, we found increased stromal DCAMKL-1 staining compared to adjacent epithelia. Within the submucosa of dysplastic BE tissues, an increase in the endothelial cell expression of DCAMKL-1 was observed. Finally, an upregulation of DCAMKL-1, LGR5, and Msi-1 mRNA was seen in BE compared to squamous NEM. Conclusions: In the present study, we report the progressive increase of DCAMKL-1 expression in BE from dysplasia to EAC. Furthermore, there was an increase in putative stem cell markers DCAMKL-1, LGR5, and Msi-1 mRNA. Taken together, these data suggest that the regulation of resident stem cells might play an important role in the progression of BE to EAC.

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KW - Cancer

KW - Doublecortin and CaM kinase-like-1

KW - Esophageal adenocarcinoma

KW - Esophagus

KW - Leucine-rich repeat-containing G-protein-coupled receptor

KW - Musashi-1

KW - Stem cell marker

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