EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors.
BACKGROUND
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.


METHODS
37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology.


RESULTS
Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was 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.


CONCLUSIONS
We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.
Kothmaier
H
H
Institute of Pathology, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 25, A-8036 Graz, Austria.
Quehenberger
F
F
Halbwedl
I
I
Morbini
P
P
Demirag
F
F
Zeren
H
H
Comin
C E
CE
Murer
B
B
Cagle
P T
PT
Attanoos
R
R
Gibbs
A R
AR
Galateau-Salle
F
F
Popper
H H
HH
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002450:Cell Communication; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008654:Mesothelioma / Q000401:mortality / Q000473:pathology*; D046228:Microarray Analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010997:Pleural Neoplasms / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor