Intercellular adhesion molecule-1 expression by bladder cancer cells: functional effects.
The role of intercellular adhesion molecule-1 (ICAM-1) and its ligand, leukocyte function-associated antigen-1 (LFA-1), in the interaction between bladder cancer cells and lymphokine activated killer (LAK) cells was investigated. Expression and modulation of ICAM-1 by cytokine treatment was assessed by immunocytometry and Northern blot analysis. Four of five human bladder cancer cell lines expressed ICAM-1 constitutively and responded to cytokine stimulation. Expression of ICAM-1 was upregulated most consistently by treatment with interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha), cytokines that are released into the urine after intravesical BCG treatment. In contrast, interleukin-1 and phorbol myristate acetate exhibited variable effects on ICAM-1 expression, and interferon-alpha had no effect. The adherence of LAK cells to bladder cancer cell monolayers and LAK cell-mediated cytolysis were then studied. Monoclonal antibodies to ICAM-1 and LFA-1 significantly decreased the binding of LAK cells to the cell lines that express ICAM-1 (37 to 75% reduction, p < 0.05), and cytokine treatment (IFN gamma, TNF alpha) of these cells enhanced ICAM-1 dependent adherence (18 to 39% increase, p < 0.05). In contrast, these manipulations had no effect on the binding of LAK cells to the UMUC3 cell line, which does not express ICAM-1. Monoclonal antibodies to LFA-1 decreased LAK cell mediated cytolysis of the bladder cancer cells from 27 to 65% (p < 0.05), but anti-ICAM-1 antibodies were much less effective (0 to 25% decrease in cytolysis). Cytokine treatment (IFN gamma, TNF alpha) of the tumor cells did not significantly increase LAK cell-mediated cytolysis, despite upregulation of ICAM-1. These data demonstrate that ICAM-1 plays a role in the binding of LAK cells to bladder cancer cells but is only marginally involved in the process of LAK cell-mediated cytolysis. These findings suggest that adhesion molecules may be important mediators of the immune response to bladder cancer after intravesical BCG therapy.
Campbell
S C
SC
Department of Urology, Cleveland Clinic Foundation, Ohio 44195.
Tanabe
K
K
Alexander
J P
JP
Edinger
M
M
Tubbs
R R
RR
Klein
E A
EA
D015152:Blotting, Northern; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate