1. Characterization of periostin isoform pattern in non-small cell lung cancer
- Author
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Adriana von Teichman, Holger Moch, Markus Rechsteiner, Alex Soltermann, Laura Morra, Silvia Casagrande, Peter Schraml, University of Zurich, and Soltermann, A
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Cancer Research ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,Vimentin ,610 Medicine & health ,Laser Capture Microdissection ,Biology ,Periostin ,Metastasis ,Cohort Studies ,10049 Institute of Pathology and Molecular Pathology ,Carcinoma, Non-Small-Cell Lung ,medicine ,Biomarkers, Tumor ,Humans ,Protein Isoforms ,1306 Cancer Research ,Epithelial–mesenchymal transition ,RNA, Messenger ,Lung cancer ,Lung ,Laser capture microdissection ,Aged ,Aged, 80 and over ,Cancer ,Epithelial Cells ,Middle Aged ,medicine.disease ,Molecular biology ,Immunohistochemistry ,Oncology ,2740 Pulmonary and Respiratory Medicine ,biology.protein ,2730 Oncology ,Stromal Cells ,Cell Adhesion Molecules - Abstract
The extracellular matrix N-glycoprotein periostin (OSF-2, POSTN) is a major constituent of the desmoplastic stroma around solid tumors. It promotes tumor invasion and metastasis via epithelial-mesenchymal transition (EMT). In this study we investigated periostin expression at both RNA and protein level as well as the expression pattern of its splice isoforms in non-small cell lung cancer (NSCLC).Thirty fresh frozen and corresponding formalin-fixed NSCLC tissues (adeno- and squamous cell carcinoma subtype, each n=15) and their matched non-neoplastic tissues were investigated. Periostin mRNA levels were analyzed by quantitative RT-PCR. The EMT-markers periostin and vimentin were analyzed by immunohistochemistry. Laser capture microdissection allowed for analysis of periostin expression in tumor epithelia and stroma, separately. Isoform patterns were investigated by isoform-specific PCR following sequencing in NSCLC, fetal and adult normal lung tissue.The qRT-PCR analysis showed periostin mRNA up-regulation in NSCLC tissue in relation to normal lung, with significantly higher levels in the adeno-compared to the squamous cell subtype (p0.05). However, protein levels in both tumor epithelia and stroma correlated with squamous cell carcinoma (p0.001) and larger tumor size (p0.05). Further, periostin tumor epithelia expression, correlated with higher tumor grade (p0.05). Sequence analysis detected eight periostin isoforms in fetal lung, but only five in both NSCLC and matched normal lung tissue. Among the eight isoforms, four are new and were labelled 5, 7, 8 and 9. The exclusive presence of isoforms 1 and 9 in fetal tissue suggests splice-specific regulation during lung embryogenesis. Finally, laser capture microdissection demonstrated that both tumor epithelia and stromal cells can be a source of periostin production in NSCLC.This study represents the first analysis of periostin isoform expression patterns in NSCLC and a characterization of periostin expression in cancer versus stromal cells at both RNA and protein level.
- Published
- 2011