Tumor-microenvironment interactions studied by zonal transcriptional profiling of squamous cell lung carcinoma

被引:9
|
作者
Wu, Hui [1 ]
Haag, Daniel [1 ]
Muley, Thomas [2 ,3 ]
Warth, Arne [4 ]
Zapatka, Marc [1 ]
Toedt, Grischa [1 ]
Pscherer, Armin [1 ]
Hahn, Meinhard [1 ]
Rieker, Ralf J. [4 ,5 ]
Wachter, David L. [5 ]
Meister, Michael [2 ,3 ]
Schnabel, Philipp [4 ]
Mueller-Decker, Karin [6 ]
Rogers, Michael A. [1 ]
Hoffmann, Hans [2 ]
Lichter, Peter [1 ]
机构
[1] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany
[2] Univ Klinikum Heidelberg, Thoraxklin, Heidelberg, Germany
[3] Translat Lung Res Ctr TLRC H, Heidelberg, Germany
[4] Univ Hosp, Inst Pathol, Heidelberg, Germany
[5] Univ Hosp, Inst Pathol, Erlangen, Germany
[6] German Canc Res Ctr, Core Facil Tumor Models, D-69120 Heidelberg, Germany
来源
GENES CHROMOSOMES & CANCER | 2013年 / 52卷 / 03期
关键词
JUNCTIONAL ADHESION MOLECULE; PROSTAGLANDIN E-2; GENE-EXPRESSION; MICRORNA EXPRESSION; PREDICTS SURVIVAL; UP-REGULATION; CANCER; RECEPTOR; PROTEIN; MICROARRAYS;
D O I
10.1002/gcc.22025
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Invasion is a critical step in lung tumor progression. The interaction between tumor cells and their surroundings may play an important role in tumor invasion and metastasis. To better understand the mechanisms of tumor invasion and tumormicroenvironment interactions in lung tumors, total RNA was isolated from the inner tumor, tumor invasion front, adjacent lung, and distant normal lung tissue from 17 patients with primary squamous cell lung carcinoma using punch-aided laser capture microdissection. Messenger RNA expression profiles were obtained by microarray analysis, and microRNA profiles were generated from eight of these samples using TaqMan Low Density Arrays. Statistical analysis of the expression data showed extensive changes in gene expression in the inner tumor and tumor front compared with the normal lung and adjacent lung tissue. Only a few genes were differentially expressed between tumor front and the inner tumor. Several genes were validated by immunohistochemistry. Evaluation of the microRNA data revealed zonal expression differences in nearly a fourth of the microRNAs analyzed. Validation of selected microRNAs by in situ hybridization demonstrated strong expression of hsa-miR-196a in the inner tumor; moderate expression of hsa-miR-224 in the inner tumor and tumor front, and strong expression of hsa-miR-650 in the adjacent lung tissue. Pathway analysis placed the majority of genes differentially expressed between tumor and nontumor cells in intrinsic processes associated with inflammation and extrinsic processes related to lymphocyte physiology. Genes differentially expressed between the inner tumor and the adjacent lung/normal lung tissue affected pathways of arachidonic acid metabolism and eicosanoid signaling. (c) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:250 / 264
页数:15
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