The mucinous domain of pancreatic carboxyl-ester lipase (CEL) contains core 1/core 2 O- glycans that can be modified by ABO blood group determinants

J Biol Chem. 2018 Dec 14;293(50):19476-19491. doi: 10.1074/jbc.RA118.001934. Epub 2018 Oct 12.


Carboxyl-ester lipase (CEL) is a pancreatic fat-digesting enzyme associated with human disease. Rare mutations in the CEL gene cause a syndrome of pancreatic exocrine and endocrine dysfunction denoted MODY8, whereas a recombined CEL allele increases the risk for chronic pancreatitis. Moreover, CEL has been linked to pancreatic ductal adenocarcinoma (PDAC) through a postulated oncofetal CEL variant termed feto-acinar pancreatic protein (FAPP). The monoclonal antibody mAb16D10 was previously reported to detect a glycotope in the highly O-glycosylated, mucin-like C terminus of CEL/FAPP. We here assessed the expression of human CEL in malignant pancreatic lesions and cell lines. CEL was not detectably expressed in neoplastic cells, implying that FAPP is unlikely to be a glycoisoform of CEL in pancreatic cancer. Testing of the mAb16D10 antibody in glycan microarrays then demonstrated that it recognized structures containing terminal GalNAc-α1,3(Fuc-α1,2)Gal (blood group A antigen) and also repeated protein sequences containing GalNAc residues linked to Ser/Thr (Tn antigen), findings that were supported by immunostainings of human pancreatic tissue. To examine whether the CEL glycoprotein might be modified by blood group antigens, we used high-sensitivity MALDI-TOF MS to characterize the released O-glycan pool of CEL immunoprecipitated from human pancreatic juice. We found that the O-glycome of CEL consisted mainly of core 1/core 2 structures with a composition depending on the subject's FUT2 and ABO gene polymorphisms. Thus, among digestive enzymes secreted by the pancreas, CEL is a glycoprotein with some unique characteristics, supporting the view that it could serve additional biological functions to its cholesteryl esterase activity in the duodenum.

Keywords: ABO blood group; BSDL; CEL; O-glycans; Tn antigen; carboxyl-ester lipase; glycomics; glycoprotein; immunohistochemistry; lipase; pancreas; pancreatic cancer; pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / metabolism*
  • Carboxylesterase / chemistry*
  • Carboxylesterase / metabolism*
  • Cell Line, Tumor
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Pancreas / enzymology*
  • Polysaccharides / metabolism*
  • Protein Domains


  • ABO Blood-Group System
  • Polysaccharides
  • Carboxylesterase