Antibodies to a CA 19-9 Related Antigen Complex Identify SOX9 Expressing Progenitor Cells In Human Foetal Pancreas and Pancreatic Adenocarcinoma

Sci Rep. 2019 Feb 27;9(1):2876. doi: 10.1038/s41598-019-38988-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Antibodies, Neoplasm / chemistry*
  • CA-19-9 Antigen / metabolism*
  • Cell Line
  • Fetus / metabolism*
  • Fetus / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Proteins / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Pancreas / embryology
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • SOX9 Transcription Factor / metabolism*

Substances

  • Antibodies, Neoplasm
  • CA-19-9 Antigen
  • Neoplasm Proteins
  • SOX9 Transcription Factor
  • SOX9 protein, human