biostudies-literatureClausen TMby Novo Nordisk FoundationBLRD VAU.S. Dept of Veterans AffairsNational Institutes of Health SIG grantNHLBI NIH HHSNIHThe Novo Nordisk FoundationNHLBINCI Research SpecialistNCI NIH HHSCancer Research Coordinating CommitteeNIGMS NIH HHSNIH HHSNIGMSRuth L. Kirschstein National Research Service Awarde184172https://www.ebi.ac.uk/biostudies/studies/S-EPMC12618072biostudies-literatureUnknown135(22)3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid. Here, we show that HSAT is ubiquitously expressed in the basement membranes of epithelial cells in multiple tissues. In the pancreas, HSAT is expressed by healthy ductal cells, and its expression is increased in premalignant pancreatic intraepithelial neoplasia lesions but not in pancreatic ductal adenocarcinoma (PDAC). Inactivation of HS3ST1, a key enzyme in HSAT synthesis, in PDAC cells eliminated HSAT expression, inducedThe Journal of clinical investigationAntithrombin-binding heparan sulfate is ubiquitously expressed in epithelial cells and suppresses pancreatic tumorigenesis.PMC12618072I01-BX003688-05A2R21 HL167091P01 HL131474C23CR5578R35 CA197699P30 CA23100T32 GM007752NNF22OC0076899R35-GM150736R35 GM150736R21-HL167091NNF22OC0073736U01 CA233581I01 BX003688S10 OD026929F31 CA247489HL131474P30 CA023100R35 GM119850R50 CA211462Joshi HJCoker JAicher AWang GDawson DWEsko JDEngle DDWeiss RJCaffrey TCDworkin LAPeck KLLewis NEChang IMLe DHollingsworth MAMoores AClausen TMSander MChen TRodriguez JPFuster MMGrandgenett PMKellman BPBhalerao NBellis SLFerguson LPGrem JLSong HPadala VMiller RLSandoval DRReya TTremblay JROgawa SKarlsson RHeeschen CfalseAntithrombin-binding heparan sulfate is ubiquitously expressed in epithelial cells and suppresses pancreatic tumorigenesis.3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid. Here, we show that HSAT is ubiquitously expressed in the basement membranes of epithelial cells in multiple tissues. In the pancreas, HSAT is expressed by healthy ductal cells, and its expression is increased in premalignant pancreatic intraepithelial neoplasia lesions but not in pancreatic ductal adenocarcinoma (PDAC). Inactivation of HS3ST1, a key enzyme in HSAT synthesis, in PDAC cells eliminated HSAT expression, induced2025-01-01T00:00:00Z2025 Nov2026-07-15T13:49:39.264Z2026-07-05T03:11:10.416ZS-EPMC126180724092447410.1172/JCI184172