Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer.
Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer.
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发表时间：
1999-06
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通讯作者：
Zhong Chen;Pramit S. Malhotra;G. Thomas;F. Ondrey;D. Duffey;Conrad W. Smith;Ileana I. Enamorado
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作者：
Zhong Chen;Pramit S. Malhotra;G. Thomas;F. Ondrey;D. Duffey;Conrad W. Smith;Ileana I. Enamorado
在头颈部鳞状细胞癌(HNSCC)患者中观察到免疫、炎症和血管生成反应的改变，其中许多反应与侵袭性恶性行为和预后的下降有关。在这项研究中，我们检验了HNSCC细胞产生调节免疫、炎症和血管生成反应的细胞因子的假设。我们通过ELISA法在明确定义的和新鲜培养的HNSCC细胞系的上清中鉴定了重要的调节细胞因子，并通过免疫组织化学方法确定这些细胞因子是否在肿瘤细胞系和组织标本中检测到。测定HNSCC患者血清细胞因子及细胞因子依赖的急性期炎症反应(纤维蛋白原、C反应蛋白、血沉)浓度，并分析血清细胞因子水平与肿瘤体积的关系。在一组已建立的密歇根大学鳞状细胞癌(UM-SCC)细胞系的上清和新鲜分离的原代HNSCC培养上清液中检测到相似浓度范围的细胞因子IL-1α、IL-6、IL-8、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子。免疫组织化学方法原位检测肿瘤标本中HNSCC细胞表达IL-1α、IL-6、IL-8、粒细胞-巨噬细胞集落刺激因子和血管内皮生长因子。在对血清中细胞因子水平和细胞因子诱导的急性时相蛋白进行前瞻性比较中，我们报告了HNSCC患者血清中细胞因子IL-6、IL-8和VEGF的浓度高于喉乳头状瘤患者或年龄匹配的对照组(P<；0.05)。血清IL-8和VEGF浓度与原发肿瘤体积大的相关性较弱(R2分别为0.2和0.4)。IL-1和IL-6诱导的急性时相反应在癌症患者中也被检测到升高，但在乳头状瘤患者或对照组中未检测到(P<；0.05)。因此，我们得出结论，在促炎症和促血管生成反应中重要的细胞因子在HNSCC患者的细胞系、组织标本和血清中都可以检测到。这些细胞因子可能会增加HNSCC的致病性，并被证明是有用的生物标志物或治疗靶点。
Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma (HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry. The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses (i.e., fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin (IL)-1alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma (UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0.05). The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R2 = 0.2 and 0.4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients but not in patients with papilloma or control subjects (at P < 0.05). We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC and prove useful as biomarkers or targets for therapy.