Phenotypic differences of proliferating fibroblasts in the stroma of lung adenocarcinoma and normal bronchus tissue
Phenotypic differences of proliferating fibroblasts in the stroma of lung adenocarcinoma and normal bronchus tissue
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DOI：
10.1111/j.1349-7006.2004.tb02207.x
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发表时间：
2004-03-01
期刊：
影响因子：
5.7
通讯作者：
Noguchi, M
中科院分区：
文献类型：
--
作者：
Nakamura, N;Iijima, T;Noguchi, M
肿瘤组织中的成纤维细胞被认为与肿瘤细胞直接和/或间接相互作用，在肿瘤的侵袭和转移中起重要作用。为了表征肺腺癌中增殖成纤维细胞的表型，我们从同一患者的正常支气管和腺癌组织中建立了短期成纤维细胞系，并比较了基因表达谱。在分析中使用了四组成纤维细胞系（总共八个细胞系）。从每个细胞系中提取总RNA，并与在cDNA过滤器阵列上印迹的550个癌症相关RNA杂交。与正常支气管成纤维细胞相比，在肿瘤组织成纤维细胞系中检测到5个上调基因和12个下调基因（共17个基因）。使用实时定量RT-PCR方法，每个基因的表达谱进行了检查; 5个基因，一个上调（MLH 1）和4个下调（Cox 1，FGFR 4，p120和Smad 3），被确认。同时，采用免疫组化法检测了5个基因在癌组织和正常组织中的蛋白表达水平，并在体内证实了MLH 1在癌组织中的上调和Cox 1的下调。这些结果表明，肺腺癌中增殖的成纤维细胞与正常支气管组织中的成纤维细胞在表型上不同。
Fibroblasts in tumor tissue are thought to interact with tumor cells directly and/or indirectly and to have important roles in tumor invasion and metastasis. To characterize the phenotype of proliferating fibroblasts in pulmonary adenocarcinoma, we established short-term fibroblast cell lines from both normal bronchus and adenocarcinoma tissues obtained from the same patients and compared the gene expression profiles. Four sets of fibroblast cell lines (eight cell lines in total) were used in the analysis. Total RNA was extracted from each cell line and hybridized with 550 cancer-related RNAs blotted on a cDNA filter array. Five up-regulated genes and 12 down-regulated genes (total of 17 genes) were detected in the fibroblast cell lines from the tumor tissues compared with those from normal bronchus. Using real-time quantitative RT-PCR methods, the expression profile of each gene was examined; five genes, one up-regulated (MLH1) and four down-regulated (Cox1, FGFR4, p120, and Smad3), were confirmed. Furthermore, the protein expression levels of the five genes in the cancerous and normal tissues were examined immunohistochemically, and the up-regulation of MLH1 and the down-regulation of Cox1 in cancerous tissue were confirmed in vivo. These results indicate that the proliferating fibroblasts in pulmonary adenocarcinomas are phenotypically different from fibroblasts in normal bronchus tissues.