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

Abstract

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.

• Authors: Hui Wu, Daniel Haag, Thomas Muley, Arne Warth, Marc Zapatka, Grischa Toedt, Armin Pscherer, Meinhard Hahn, Ralf J Rieker, David L Wachter, Michael Meister, Philipp Schnabel, Karin Müller-Decker, Michael A Rogers, Hans Hoffmann, Peter Lichter
• Journal: Genes, chromosomes & cancer (Genes Chromosomes Cancer) Vol. 52 Issue 3 Pg. 250-64 (Mar 2013) ISSN: 1098-2264 [Electronic] United States
• PMID: 23074073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• MicroRNAs

Topics

• Carcinoma, Squamous Cell (genetics, pathology)
• Cluster Analysis
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, pathology)
• MicroRNAs (genetics)
• Reproducibility of Results
• Transcriptome
• Tumor Microenvironment (genetics)