Role of adhesion molecules in lymphokine-activated killer cell killing of bladder cancer cells: further evidence for a third ligand for leucocyte function-associated antigen-1.
The lysis of eight human bladder cancer cell lines by lymphokine-activated killer cells (LAK) was found to be partially dependent upon the expression by the target cell of either intercellular adhesion molecule-1 (ICAM-1) or intercellular adhesion molecule-2 (ICAM-2). Using adhesion blockade studies these molecules were found to contribute towards sensitivity to lysis. Tumour lines of low grade (G1) did not constitutively express ICAM-1, but were found to express ICAM-2. High grade cells (G2, G3), however, only constitutively expressed ICAM-1 on their cell surface. Interferon-gamma (IFN-gamma) induced and augmented the expression of ICAM-1 by all except one of the cell lines (UMUC3) in a dose- and time-dependent manner. This was accompanied by an increased susceptibility to lymphokine-activated killer mediated cytolysis. Anti-ICAM-1 antibodies partially inhibited the increase in cell lysis due to IFN-gamma. However, this inhibition was not complete. When effector cells were treated with antibodies to leucocyte function-associated antigen-1 (LFA-1) the inhibition of lysis was greater and ranged from 72 to 96% with a mean of 87% inhibition. These results suggest that the increased sensitivity of IFN-gamma-treated bladder cancer cell lines to LAK cells is partially attributable to the induction of ICAM-1. However, blocking of ICAM-1 with antibodies could only partially inhibit the increased LFA-1-dependent lysis. This supports recent evidence for the existence of an additional ligand for LFA-1, other than ICAM-1 and ICAM-2.
Department of Surgery/Urology, University of Edinburgh Medical School, U.K.
A M
AM
Jackson
A B
AB
Alexandrov
S
S
Prescott
K
K
James
G D
GD
Chisholm
D015703:Antigens, CD; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000276:immunology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma