Osteopontin is linked to p65 and MMP-9 expression in pulmonary adenocarcinoma but not in malignant pleural mesothelioma.
OBJECTIVE
Osteopontin (OPN) is a matricellular protein involved in tissue remodelling, cell-mediated immunity and malignant transformation. High OPN serum levels predict poor prognosis in non-small cell carcinoma and set patients with malignant pleural mesothelioma (MM) apart from disease-free asbestos-exposed individuals. Yet neither the spectrum of tissue expression nor the signalling pathways of OPN in MM and pulmonary adenocarcinoma have been characterized, although in vitro evidence links OPN to the epidermal growth factor receptor (EGFR) pathway. The aim of this study was to address these deficiencies.


RESULTS
OPN expression was investigated immunohistochemically in 104 adenocarcinomas and 38 MM and correlated with histological features, including tumour type, grade and proliferation and with expression of activated intermediary EGFR signalling pathway molecules p65, p-AKT, p-ERK, p-STAT-3, and of metalloproteinase (MMP)-1, MMP-2 and MMP-9. In MM, OPN expression was widespread (36/38) and independent of the molecular parameters studied. In adenocarcinoma, high OPN expression was correlated with expression of p65, p-ERK and MMP-9.


CONCLUSIONS
Frequent OPN expression is typical of, but not specific for MM, whereas it appears to select adenocarcinoma cases with p65 and MMP-9 expression, suggesting a link with EGFR signalling pathways.
Frey
A B
AB
Department of Pathology, Harper University Hospital, and Karmanos Cancer Institute, 3990 John R. Street, Detroit, MI 48201, USA.
Wali
A
A
Pass
H
H
Lonardo
F
F
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003937:Diagnosis, Differential; D066246:ErbB Receptors / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008654:Mesothelioma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D010997:Pleural Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051996:Transcription Factor RelA; D053495:Osteopontin; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9