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 b etween bladder cancer cells and lymphokine activated killer (LAK) cell s was investigated. Expression and modulation of ICAM-1 by cytokine tr eatment was assessed by immunocytometry and Northern blot analysis. Fo ur of five human bladder cancer eel lines expressed ICAM-1 constitutiv ely and responded to cytokine stimulation. Expression of ICAM-1 was up regulated most consistently by treatment with interferon-gamma (IFN ga mma) and tumor necrosis factor-alpha (TNF alpha), cytokines that are r eleased 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 adheren ce of LAK cells to bladder cancer cell monolayers and LAK cell-mediate d 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 treat ment (IFN gamma, TNF alpha) of these cells enhanced ICAM-1 dependent a dherence (18 to 39% increase, p <0.05). In contrast, these manipulatio ns had no effect on the binding of LAK cells to the UMUC3 cell line, w hich 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 c ytolysis, despite upregulation of ICAM-1. These data demonstrate that ICAM-1 plays a role in the binding of LAK cells to bladder cancer cell s but is only marginally involved in the process of LAK cell-mediated cytolysis. These findings suggest that adhesion molecules may be impor tant mediators of the immune response to bladder cancer after intraves ical BCG therapy.