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

J Cell Biochem. 1996 Mar 15;60(4):538-49. doi: 10.1002/(SICI)1097-4644(19960315)60:4%3C538::AID-JCB10%3E3.0.CO;2-D.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / physiology*
  • Antigens, Tumor-Associated, Carbohydrate / immunology
  • Cell Adhesion / immunology
  • Colonic Neoplasms / immunology*
  • Cytoplasm
  • E-Selectin / analysis*
  • Endothelium, Vascular / chemistry
  • Epitopes / immunology*
  • HL-60 Cells
  • Humans
  • Leukocytes / immunology
  • Lewis Blood Group Antigens / immunology*
  • Lewis X Antigen / immunology
  • Mucin-1 / immunology
  • Mucin-1 / physiology*
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Antigens, Tumor-Associated, Carbohydrate
  • E-Selectin
  • Epitopes
  • Lewis Blood Group Antigens
  • Lewis X Antigen
  • Mucin-1