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
© 2018 El Jellas et al..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:293 |
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| Enthalten in: |
The Journal of biological chemistry - 293(2018), 50 vom: 14. Dez., Seite 19476-19491 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
El Jellas, Khadija [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.04.2019 Date Revised 05.02.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1074/jbc.RA118.001934 |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a El Jellas, Khadija |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a 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 |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 09.04.2019 | ||
| 500 | |a Date Revised 05.02.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 El Jellas et al. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ABO blood group | |
| 650 | 4 | |a BSDL | |
| 650 | 4 | |a CEL | |
| 650 | 4 | |a O-glycans | |
| 650 | 4 | |a Tn antigen | |
| 650 | 4 | |a carboxyl-ester lipase | |
| 650 | 4 | |a glycomics | |
| 650 | 4 | |a glycoprotein | |
| 650 | 4 | |a immunohistochemistry | |
| 650 | 4 | |a lipase | |
| 650 | 4 | |a pancreas | |
| 650 | 4 | |a pancreatic cancer | |
| 650 | 4 | |a pathology | |
| 650 | 7 | |a ABO Blood-Group System |2 NLM | |
| 650 | 7 | |a Polysaccharides |2 NLM | |
| 650 | 7 | |a Carboxylesterase |2 NLM | |
| 650 | 7 | |a EC 3.1.1.1 |2 NLM | |
| 700 | 1 | |a Johansson, Bente B |e verfasserin |4 aut | |
| 700 | 1 | |a Fjeld, Karianne |e verfasserin |4 aut | |
| 700 | 1 | |a Antonopoulos, Aristotelis |e verfasserin |4 aut | |
| 700 | 1 | |a Immervoll, Heike |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Man H |e verfasserin |4 aut | |
| 700 | 1 | |a Hoem, Dag |e verfasserin |4 aut | |
| 700 | 1 | |a Lowe, Mark E |e verfasserin |4 aut | |
| 700 | 1 | |a Lombardo, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a Njølstad, Pål R |e verfasserin |4 aut | |
| 700 | 1 | |a Dell, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Mas, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Haslam, Stuart M |e verfasserin |4 aut | |
| 700 | 1 | |a Molven, Anders |e verfasserin |4 aut | |
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