Carcinogenesis Advance Access originally published online on September 24, 2004
Carcinogenesis 2005 26(1):17-25; doi:10.1093/carcin/bgh276
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis vol.26 no.1 © Oxford University Press 2005; all rights reserved.
ARTICLE |
L1CAM, INP10, P-cadherin, tPA and ITGB4 over-expression in malignant pleural mesotheliomas revealed by combined use of cDNA and tissue microarray
1 Department of Pathology and Department of Medical Genetics, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 2 Department of Histopathology, Royal Brompton Hospital, London, UK, 3 Department of Occupational Medicine and Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland, 4 Laboratory of Computer and Information Science, Helsinki University of Technology, Espoo, Finland and 5 Department of Internal Medicine, Division of Pulmonary Diseases, Helsinki University Central Hospital, Helsinki, Finland
6 To whom correspondence should be addressed Email: sakari.knuutila{at}helsinki.fi
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 ß4 (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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y C G. Lee Hunting for a pleural fluid test for mesothelioma: is soluble mesothelin the answer? Thorax, July 1, 2007; 62(7): 561 - 562. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lopez-Rios, S. Chuai, R. Flores, S. Shimizu, T. Ohno, K. Wakahara, P. B. Illei, S. Hussain, L. Krug, M. F. Zakowski, et al. Global Gene Expression Profiling of Pleural Mesotheliomas: Overexpression of Aurora Kinases and P16/CDKN2A Deletion as Prognostic Factors and Critical Evaluation of Microarray-Based Prognostic Prediction. Cancer Res., March 15, 2006; 66(6): 2970 - 2979. [Abstract] [Full Text] [PDF]
|
|