A lymph node metastatic mouse model reveals alterations of metastasis-related gene expression in metastatic human oral carcinoma sublines selected from a poorly metastatic parental cell line
A lymph node metastatic mouse model reveals alterations of metastasis-related gene expression in metastatic human oral carcinoma sublines selected from a poorly metastatic parental cell line
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作者：
Zhang, X;Liu, YN;Chen, Z
背景超过40%的口腔鳞状细胞癌（SCC）患者在诊断时有淋巴结转移，5年生存率低于50%。调节SCC向淋巴结转移的基因表达的变化尚未确定。为了研究口腔SCC的转移，使用淋巴结转移小鼠模型通过体内选择从低转移性口腔SCC细胞系建立高转移性口腔SCC细胞系。使用Matrigel侵袭和细胞表面蛋白粘附测定来研究细胞的转移潜力。采用北方印迹分析、免疫印迹、基因表达快速分析和cDNA微阵列技术检测转移衍生物及其亲本细胞中转移相关基因编码的mRNA和蛋白质。体内选择的转移性细胞显示出比亲本细胞高得多的Matrigel侵袭能力。它们还显示出对三种细胞表面蛋白的粘附特性的改变。转移和非转移细胞的比较显示转移相关基因表达的几个显著变化，包括尿激酶型纤溶酶原激活物受体，整合素01，膜型1-基质金属蛋白酶的上调，和蛋白酶激活受体-1的下调。据作者所知，目前的研究是第一个报告基因表达分析使用淋巴结转移小鼠模型的人口腔鳞状细胞癌。这些数据表明，转移相关基因表达的某些改变有利于口腔鳞癌的侵袭，细胞表面蛋白可能在口腔鳞癌向淋巴结转移中发挥重要作用。(C)2002年美国癌症协会。
BACKGROUND. Greater than 40% of patients with squamous cell carcinoma (SCC) of the oral cavity have lymph node metastasis at the time of diagnosis and a 5-year survival rate of less than 50%. Changes in gene expression that regulate metastasis of SCC to lymph nodes have not been identified.METHODS. To study metastasis of oral SCC, highly metastatic oral SCC cell lines from a poorly metastatic oral SCC cell line were established by in vivo selection using a lymph node metastatic mouse model. The metastatic potential of the cells was studied using Matrigel invasion and cell surface protein adhesion assays. mRNA and protein encoded from metastasis-related genes in the metastatic derivatives and in their parental cells were examined using Northern blot analysis, immunoblotting, rapid analysis of gene expression, and a cDNA microarray technique.RESULTS. The in vivo selected metastatic cells showed much higher Matrigel invasion capability than the parental cells. They also showed alterations in their adhesion properties to three cell surface proteins. Comparison of metastatic and nonmetastatic cells revealed several significant alterations in the expression of metastasis-related genes, including up-regulation of the urokinase-type plasminogen activator receptor, integrin 01, membrane type 1-matrix metalloprotemase, and down-regulation of protease-activated receptor-1.Conclusions. To the authors' knowledge, the current study is the first to report on gene expression analysis using a lymph node metastatic mouse model of human oral SCC. The data suggest that certain alterations of metastasis-related gene expression favor invasion of oral SCC and that cell surface proteins may play major roles in the metastasis of oral SCC to the lymph nodes. (C) 2002 American Cancer Society.