Inhibition of the O-glycan elongation limits MUC1 incorporation to cell membrane of human endometrial carcinoma cells.
We have studied how benzyl-N-acetyl-alpha-D-galactosaminide, O-glycosylation inhibitor, affects the polymorphism and shedding of membrane-bound MUC1 mucin, and change in adhesive properties of cancer cells. In endometrial adenocarcinoma cells (Ishikawa line), high molecular weight MUC1 mucin was shed from cellular membrane and could be detected in culture medium 24 h after [14C]threonine labelling. Short-time (2 days) exposure of these cells to benzyl-N-acetyl-alpha-D-galactosaminide was associated with a reduction in sialic acid level and increase in T antigen content in cellular MUC1 mucin. These changes could be inverted after removal of the inhibitor. A longer, 6-day action of the inhibitor induced a decrease in sialic acid and T antigen levels in cellular MUC1 mucin. Benzyl-N-acetyl-alpha-D-galactosaminide treatment caused the occurrence of a few incompletely glycosylated glycoforms of MUC1 in cells, but not in culture medium. Adhesion of endometrial cells to ECM compounds (type I collagen) was increased by benzyl-N-acetyl-alpha-D-galactosaminide treatment, indicating that glycosylation of extracellular domain of MUC1 can modulate adhesive properties of cells.
Porowska
Halina
H
Department of Medical Chemistry, Medical Academy, 15-222 Bialystok, Poland. zachemog@amb.edu.pl
Paszkiewicz-Gadek
Anna
A
Anchim
Tomasz
T
Wolczynski
Slawomir
S
Gindzienski
Andrzej
A
D000116:Acetylgalactosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D018396:Mucin-1 / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D001593:Benzyl Compounds; D024042:Collagen Type I; D018396:Mucin-1; C080739:benzyl-alpha-N-acetylgalactosamine; D000116:Acetylgalactosamine