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Tumor–microenvironment interactions studied by zonal transcriptional profiling of squamous cell lung carcinoma
Author(s) -
Wu Hui,
Haag Daniel,
Muley Thomas,
Warth Arne,
Zapatka Marc,
Toedt Grischa,
Pscherer Armin,
Hahn Meinhard,
Rieker Ralf J.,
Wachter David L.,
Meister Michael,
Schnabel Philipp,
MüllerDecker Karin,
Rogers Michael A.,
Hoffmann Hans,
Lichter Peter
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22025
Subject(s) - laser capture microdissection , biology , tumor microenvironment , microrna , pathology , tumor progression , in situ hybridization , cancer research , microdissection , gene expression , lung , gene expression profiling , lung cancer , immunohistochemistry , gene , immunology , medicine , tumor cells , biochemistry
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 tumor–microenvironment 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. © 2012 Wiley Periodicals, Inc.