Scher R L, Koch W M, Richtsmeier W J
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Md.
Arch Otolaryngol Head Neck Surg. 1993 Apr;119(4):432-8. doi: 10.1001/archotol.1993.01880160080012.
To determine if the cell surface antigen, the intercellular adhesion molecule 1 (ICAM-1), is expressed on head and neck (H&N) squamous cell carcinoma (SCC) cell lines, and if treatment with interferon gamma (IFN-gamma) enhances the expression of the antigen. Intercellular adhesion molecule 1 mediates effector cell adhesion, activation, and function in inflammatory and immunologic reactions, and it may be important in the generation of antitumor immune surveillance and cytotoxicity against H&N SCC.
Four human SCC cell lines, JHU-011-SCC, JHU-020-SCC, JHU-022-SCC, and FaDu, established by explant technique from tumors of the upper aerodigestive tract, were utilized for these experiments. The cell lines were maintained and tested under standard tissue culture conditions.
Fluorescence-activated cell sorting and enzyme-linked immunosorbent assay were performed to identify the presence of ICAM-1 on the H&N SCC cell lines after staining with an anti-ICAM-1 monoclonal antibody (CD54). The SCC cell lines were treated with either fresh media or varying dosages (1 to 1000 U/mL) of recombinant human interferon gamma (rHuIFN-gamma) to determine constitutive and enhanced antigen expression. The kinetics of the response to rHuIFN-gamma were determined for the JHU-022-SCC cell line. The effect of the cytokines interleukin 1, interleukin 2, tumor necrosis factor alpha, and interferon alfa on ICAM-1 expression on JHU-022-SCC was also tested.
Constitutive and enhanced ICAM-1 expression.
Low levels of constitutive expression of ICAM-1 were identified on all four H&N SCC cell lines, with significantly enhanced expression seen after rHuIFN-gamma treatment (P = .0001). Maximally enhanced expression of the antigen on JHU-022-SCC occurred after treatment for 48 hours with 100 U/mL of rHuIFN-gamma (P = .0001). Induction of ICAM-1 expression was detectable after treatment with as little as 10 U/mL of rHuIFN-gamma (P < .001). Induction was also present after treatment with interleukin 1 and tumor necrosis factor alpha, but not with interleukin 2 or interferon alfa.
Intercellular adhesion molecule 1 is constitutively expressed on H&N SCC cell lines, with enhanced expression seen after treatment with interferon gamma and other cytokines. This suggests that the antigen may be involved in the generation of an immune response against SCC of the H&N.
确定细胞表面抗原细胞间黏附分子1（ICAM-1）是否在头颈部（H&N）鳞状细胞癌（SCC）细胞系上表达，以及用γ干扰素（IFN-γ）治疗是否能增强该抗原的表达。细胞间黏附分子1在炎症和免疫反应中介导效应细胞的黏附、激活及功能，其可能在针对H&N SCC的抗肿瘤免疫监视和细胞毒性的产生中起重要作用。
利用通过外植技术从上下呼吸道肿瘤建立的4种人SCC细胞系JHU-011-SCC、JHU-020-SCC、JHU-022-SCC和FaDu进行这些实验。细胞系在标准组织培养条件下维持并检测。
在用抗ICAM-1单克隆抗体（CD54）染色后，进行荧光激活细胞分选和酶联免疫吸附测定，以鉴定H&N SCC细胞系上ICAM-1的存在。用新鲜培养基或不同剂量（1至1000 U/mL）的重组人γ干扰素（rHuIFN-γ）处理SCC细胞系，以确定组成性和增强性抗原表达。测定JHU-022-SCC细胞系对rHuIFN-γ反应的动力学。还检测了细胞因子白细胞介素1、白细胞介素2、肿瘤坏死因子α和α干扰素对JHU-022-SCC上ICAM-1表达的影响。
组成性和增强性ICAM-1表达。
在所有4种H&N SCC细胞系上均鉴定出低水平的ICAM-1组成性表达，rHuIFN-γ处理后表达显著增强（P = .0001）。JHU-022-SCC上抗原的最大增强表达在100 U/mL rHuIFN-γ处理48小时后出现（P = .0001）。用低至10 U/mL的rHuIFN-γ处理后即可检测到ICAM-1表达的诱导（P < .001）。白细胞介素1和肿瘤坏死因子α处理后也有诱导，但白细胞介素2或α干扰素处理后没有。
细胞间黏附分子1在H&N SCC细胞系上组成性表达，γ干扰素和其他细胞因子处理后表达增强。这表明该抗原可能参与针对H&N SCC的免疫反应的产生。
