Secreted MUC1 mucins lacking their cytoplasmic part and carrying sialyl-Lewis a and x epitopes from a tumor cell line and sera of colon carcinoma patients can inhibit HL-60 leukocyte adhesion to E-selectin-expressing endothelial cells.
A secreted MUC1 mucin from the spent medium of the colon carcinoma cell line COLO 205 carrying sialyl-Lewis a and x epitopes (H-CanAg) was purified by trichloroacetic acid precipitation and Superose 6 gel filtration. The purified H-CanAg inhibited adhesion of the leukocyte cell line HL-60 to E-selectin transfected COS-1 cells or interleukin-1 beta (IL-1 beta)-activated human umbilical vein endothelial cells. Sera from two patients with advanced colon carcinoma containing high concentrations of sialyl-Lewis a and x activity inhibited HL-60 cell adhesion to E-selectin-expressing COS-1 cells and IL-1 beta-activated endothelial cells. After affinity column absorption of the sialyl-Lewis a activity, the sera also lost most of their sialyl-Lewis x activity and at the same time their adhesion inhibitory effect. A large part of the sialyl-Lewis a/x activity in the two patients was found in fractions containing mucins having a MUC1 apoprotein, as shown by its size, and reactivity with the two anti-MUC1 apoprotein monoclonal antibodies, Ma552 and HMFG-2. The cell-adhesion inhibitory effect of the purified sialyl-Lewis a-carrying MUC1 mucin fraction from the sera of the two patients was stronger than that of smaller sized sialyl-Lewis a-carrying mucin-type glycoproteins also found in the patient sera. The MUC1 mucin fraction secreted by the COLO 205 cells and from the two sera were all shown to lack their C-terminal portion, in contrast to the MUC1 mucin from cells. It is hypothesized that sialyl-Lewis a- and/or x-containing mucins, especially MUC1, secreted by tumors can interact with E-selectin on endothelial cells and thus inhibit leukocyte adhesion.
Zhang
K
K
Department of Medical Biochemistry, University of Göteborg, Sweden.
Baeckström
D
D
Brevinge
H
H
Hansson
G C
GC
D000951:Antigens, Neoplasm / Q000276:immunology / Q000502:physiology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology*; D003593:Cytoplasm; D019040:E-Selectin / Q000032:analysis*; D004730:Endothelium, Vascular / Q000737:chemistry; D000939:Epitopes / Q000276:immunology*; D018922:HL-60 Cells; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D016256:Lewis X Antigen / Q000276:immunology; D018396:Mucin-1 / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019040:E-Selectin; D000939:Epitopes; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D018396:Mucin-1