Antibodies to a CA 19-9 Related Antigen Complex Identify SOX9 Expressing Progenitor Cells In Human Foetal Pancreas and Pancreatic Adenocarcinoma.
Adenocarcinoma
/ metabolism
Antibodies, Neoplasm
/ chemistry
CA-19-9 Antigen
/ metabolism
Cell Line
Fetus
/ metabolism
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Proteins
/ metabolism
Neoplastic Stem Cells
/ metabolism
Pancreas
/ embryology
Pancreatic Neoplasms
/ metabolism
SOX9 Transcription Factor
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 02 2019
27 02 2019
Historique:
received:
01
12
2017
accepted:
11
01
2019
entrez:
1
3
2019
pubmed:
1
3
2019
medline:
12
9
2020
Statut:
epublish
Résumé
The Sialyl Lewis A antigen, or CA 19-9, is the prototype serum biomarker for adenocarcinoma of the pancreas. Despite extensive clinical study of CA 19-9 in gastrointestinal malignancies, surprisingly little is known concerning the specific cell types that express this marker during development, tissue regeneration and neoplasia. SOX9 is a transcription factor that plays a key role in these processes in foregut tissues. We report the biochemistry and tissue expression of the GCTM-5 antigen, a pancreatic cancer marker related to, but distinct from, CA19-9. This antigen, defined by two monoclonal antibodies recognising separate epitopes on a large glycoconjugate protein complex, is co-expressed with SOX9 by foregut ductal progenitors in the developing human liver and pancreas, and in pancreatic adenocarcinoma. These progenitors are distinct from cell populations identified by DCLK1, LGR5, or canonical markers of liver and pancreatic progenitor cells. Co-expression of this antigen complex and SOX9 also characterises the ductal metaplasia of submucosal glands that occurs during the development of Barrett's oesophagus. The GCTM-5 antigen complex can be detected in the sera of patients with pancreatic adenocarcinoma. The GCTM-5 epitope shows a much more restricted pattern of expression in the normal adult pancreas relative to CA19-9. Our findings will aid in the identification, characterisation, and monitoring of ductal progenitor cells during development and progression of pancreatic adenocarcinoma in man.
Identifiants
pubmed: 30814526
doi: 10.1038/s41598-019-38988-8
pii: 10.1038/s41598-019-38988-8
pmc: PMC6393509
doi:
Substances chimiques
Antibodies, Neoplasm
0
CA-19-9 Antigen
0
Neoplasm Proteins
0
SOX9 Transcription Factor
0
SOX9 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2876Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103694
Pays : United States
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