Expression of adhesion molecules by bladder cancer cells: modulation by interferon-gamma and tumour necrosis factor-alpha.
The constitutive expression by eight human bladder cancer cell lines of the cell adhesion molecules intercellular adhesion molecule-1 and intercellular adhesion molecule-2 was studied using monoclonal antibody probes in conjunction with flow-cytometry. Tumour lines of low grade (G1) did not constitutively express intercellular adhesion molecule-1, rather they were found to express intercellular adhesion molecule-2. The G2 cells expressed no intercellular adhesion molecule-2, however, a low percentage did express intercellular adhesion molecule-1. High grade cells (G3) only expressed intercellular adhesion molecule-1 on their cell surface but at higher levels than the G2 cell line. Exposure of the bladder cancer cell lines to interferon-gamma induced and augmented the expression of intercellular adhesion molecule-1 by all except one of the cell lines (UMUC3). Intercellular adhesion molecule-2 expression remained unaltered. The modulation of intercellular adhesion molecule-1 expression was dependent on the concentration of interferon-gamma and the duration of stimulus. De novo intercellular adhesion molecule-1 expression, induced by interferon-gamma, was rapid (< 4 hours) with only a short period of stimulation being required (< 10 seconds). The rapid increase in expression of intercellular adhesion molecule-1 required de novo protein synthesis and was not the result of release of intercellular adhesion molecule-1 from an intracellular pool. Interferon-gamma and tumour necrosis factor-alpha were found to act synergistically in the induction and augmentation of intercellular adhesion molecule-1 expression. Optimal induction occurred with 10 Uml-1 of both molecules. These results suggest a correlation between constitutive adhesion molecule expression and the histopathological grade of the tumour. The implications of these findings for Bacillus Calmette Guerin and interferon-gamma immunotherapy of bladder cancer is discussed.
Jackson
A M
AM
Department of Surgery/Urology, University of Edinburgh Medical School, United Kingdom.
Alexandrov
A B
AB
Prescott
S
S
James
K
K
Chisholm
G D
GD
D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma