Malignant pleural mesothelioma (MPM) is an asbestos-related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short-term survivors (survival <3 years; STS) and long-term survivors (survival >3 years; LTS) of MPM. In order to do this, 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, anti-apoptosis, angiogenesis, and other cellular activities were investigated by tissue microarray (TMA) technology. Epidermal growth factor receptor (EGFR) is expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling is more abundant in STS. The expression of TIE2/Tek, a receptor tyrosine kinases involved in angiogenesis, is differentially regulated via PDGFR and thus is more important in STS. Anti-apoptosis is upregulated in STS by signal transducer and activator of transcription 1 (STAT1)-survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS. We demonstrate that small scale proteomics can be carried out by a powerful linkage of TMA, immunohistochemistry, and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.
- short- and long-term survivors
- signal pathways
- tissue microarray