Campbell S C, Tanabe K, Alexander J P, Edinger M, Tubbs R R, Klein E A
Department of Urology, Cleveland Clinic Foundation, Ohio 44195.
J Urol. 1994 May;151(5):1385-90. doi: 10.1016/s0022-5347(17)35265-5.
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.
研究了细胞间黏附分子-1（ICAM-1）及其配体白细胞功能相关抗原-1（LFA-1）在膀胱癌细胞与淋巴因子激活的杀伤细胞（LAK细胞）相互作用中的作用。通过免疫细胞化学和Northern印迹分析评估细胞因子处理对ICAM-1表达和调节的影响。五个人膀胱癌细胞系中有四个组成性表达ICAM-1并对细胞因子刺激有反应。用干扰素-γ（IFNγ）和肿瘤坏死因子-α（TNFα）处理最一致地上调ICAM-1的表达，这两种细胞因子在膀胱内卡介苗治疗后释放到尿液中。相反，白细胞介素-1和佛波醇肉豆蔻酸酯乙酸盐对ICAM-1表达表现出可变的影响，而干扰素-α没有作用。然后研究了LAK细胞与膀胱癌细胞单层的黏附以及LAK细胞介导的细胞溶解作用。抗ICAM-1和LFA-1的单克隆抗体显著降低LAK细胞与表达ICAM-1的细胞系的结合（降低37%至75%，p<0.05），并且这些细胞的细胞因子处理（IFNγ，TNFα）增强了ICAM-1依赖性黏附（增加18%至39%，p<0.05）。相反，这些操作对LAK细胞与不表达ICAM-1的UMUC3细胞系的结合没有影响。抗LFA-1单克隆抗体将LAK细胞介导的膀胱癌细胞溶解作用从27%降低到65%（p<0.05），但抗ICAM-1抗体的效果要差得多（细胞溶解作用降低0%至25%）。尽管ICAM-1上调，但肿瘤细胞的细胞因子处理（IFNγ，TNFα）并没有显著增加LAK细胞介导的细胞溶解作用。这些数据表明ICAM-1在LAK细胞与膀胱癌细胞的结合中起作用，但仅在LAK细胞介导的细胞溶解过程中起很小的作用。这些发现表明黏附分子可能是膀胱内卡介苗治疗后对膀胱癌免疫反应的重要介质。
