L1CAM, INP10, P-cadherin, tPA and ITGB4 over-expression in malignant pleural mesotheliomas revealed by combined use of cDNA and tissue microarray
| Autor: | Eeva Kettunen, Jouni K. Seppänen, Sakari Knuutila, Andrew G. Nicholson, Sisko Anttila, Vuokko L. Kinnula, T. Stjernvall, Jaakko Hollmén, Stig Nordling, Harriet Wikman, Bálint Nagy, Tiina Ollikainen |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Mesothelioma
Cancer Research Pathology medicine.medical_specialty DNA Complementary L1 Pleural Neoplasms Gene Expression Neural Cell Adhesion Molecule L1 Biology Cell Line 03 medical and health sciences Pleural disease 0302 clinical medicine Cell Adhesion medicine Humans Cell adhesion 030304 developmental biology 0303 health sciences Tissue microarray Reverse Transcriptase Polymerase Chain Reaction T-plasminogen activator Cell adhesion molecule Cadherin Integrin beta4 General Medicine medicine.disease Immunohistochemistry Chemokine CXCL10 Mesothelium medicine.anatomical_structure Tissue Plasminogen Activator 030220 oncology & carcinogenesis Chemokines CXC |
| Zdroj: | Carcinogenesis. 26:17-25 |
| ISSN: | 1460-2180 |
| DOI: | 10.1093/carcin/bgh276 |
| Popis: | Malignant pleural mesothelioma (MM) is a rare tumour with high mortality, which can exhibit various morphologies classified as epithelioid, biphasic and sarcomatoid subtypes. To investigate the molecular changes in these tumours, we studied gene expression patterns by combined use of cDNA arrays and tumour tissue microarrays (TMA). Deregulation of the expression of 588 cancer-related genes was screened in 16 MM comprising all three subtypes and compared with references, i.e. normal mesothelial cell lines and pleural mesothelium. Array data were analysed using three statistical methods; principal component analysis (PCA), permutation test and receiver operating characteristic (ROC) curves. Eleven genes were verified by real-time RT-PCR. Genes encoding two adhesion molecules [COL1A2 and integrin beta4 (ITGB4)] and a chemokine (INP10) were up-regulated in MM compared with both the cell lines and pleural mesothelium. There was a type-specific up-regulation of semaphorin E, ITGB4 and P-cadherin in epithelioid MM, matrix metalloproteinase 9 (MMP9) and tissue-type plasminogen activator (tPA) in sarcomatoid MM and neural cell adhesion molecule L1 (L1CAM) and INP10 in biphasic MM. Immunohistochemistry on TMA containing 47 MM (26 epithelioid, 15 sarcomatoid and six biphasic) was performed for five proteins, ITGB4, P-cadherin, tPA, INP10 and L1CAM. INP10 expression was increased in MM in general compared with normal mesothelium, while increased expression of P-cadherin, L1CAM and ITGB4 was more specific in MMs exhibiting an epithelioid growth pattern. The over-expression of tPA was more frequent in epithelioid MM despite higher mRNA levels in sarcomatoid and biphasic MM. We conclude that several proteins, associated with cell adhesion either directly (ITGB4, L1CAM, P-cadherin) or as a regulatory factor (INP10), are differentially expressed in MM. In particular, INP10, ITGB4 and COL1A2 were up-regulated in MM compared with both reference sample types, suggesting a relationship with development of these tumours. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|