Jackson A M, Alexandrov A B, Gribben S C, Esuvarnathan K, James K
Department of Surgery (WGH), University of Edinburgh Medical School, UK.
Int J Cancer. 1993 Dec 2;55(6):921-5. doi: 10.1002/ijc.2910550608.
Intercellular adhesion molecule-1 (ICAM-1) is one of 3 major ligands for the beta 2 integrin leucocyte function-associated antigen-1 (LFA-1). Several reports have emerged describing soluble forms of ICAM-1 in association with normal and pathological states (e.g., malignancy). In this study we have identified the secretion of soluble ICAM-1 in tissue culture supernatants from bladder tumour monolayers and in the urine of patients receiving intravesical BCG immunotherapy for superficial bladder cancer. In vitro, small amounts of sICAM-1 were detected in the tissue culture supernatants of bladder cancer cells, known to constitutively express ICAM-1. Following stimulation with interferon gamma, the levels of sICAM-1 increased inversely to the levels of cell surface ICAM-1, suggesting sheeding. Induction and augmentation of cell surface ICAM-1 required de novo mRNA and protein synthesis. However, treatment with cycloheximide, after stimulation with IFN-gamma, resulted in increased levels of membrane associated ICAM-1. Correspondingly, the level of sICAM-1 in the supernatant was low in comparison with controls, suggesting that cycloheximide acted via stabilization of membrane ICAM-1 or via prevention of some enzymatic cleavage event. In vivo, sICAM-1 can be detected at high levels in patients' urine following immunotherapy of bladder cancer with intravesically administered BCG organisms. Production of sICAM-1 is transient and occurs only in the first 12 hr following installation. Furthermore, production of sICAM-1 is heterogeneous as some patients fail to produce any at all. If the source of sICAM-1 is the bladder tumour per se, then its detection in urine could indicate a response of the tumour to immunotherapy and indeed may prove a useful indicator of clinical response.
细胞间黏附分子-1（ICAM-1）是β2整合素白细胞功能相关抗原-1（LFA-1）的3种主要配体之一。已有多篇报道描述了与正常和病理状态（如恶性肿瘤）相关的可溶性ICAM-1形式。在本研究中，我们在膀胱肿瘤单层组织培养上清液以及接受浅表性膀胱癌膀胱内卡介苗免疫治疗患者的尿液中鉴定出了可溶性ICAM-1的分泌。在体外，已知组成性表达ICAM-1的膀胱癌细胞的组织培养上清液中检测到少量sICAM-1。用γ干扰素刺激后，sICAM-1水平与细胞表面ICAM-1水平呈反比增加，提示有脱落现象。细胞表面ICAM-1的诱导和增强需要从头合成mRNA和蛋白质。然而，在IFN-γ刺激后用放线菌酮处理，导致膜相关ICAM-1水平升高。相应地，与对照组相比，上清液中sICAM-1水平较低，提示放线菌酮通过稳定膜ICAM-1或通过防止某些酶切事件起作用。在体内，膀胱内给予卡介苗生物制剂免疫治疗膀胱癌后，患者尿液中可检测到高水平的sICAM-1。sICAM-1的产生是短暂的，仅在灌注后的前12小时出现。此外，sICAM-1的产生存在异质性，因为有些患者根本不产生。如果sICAM-1的来源是膀胱肿瘤本身，那么在尿液中检测到它可能表明肿瘤对免疫治疗有反应，并且确实可能成为临床反应的有用指标。
