Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma.
Hepatocyte growth factor/scatter factor (HGF/SF) stimulates cell proliferation, motility and invasiveness via its receptor c-Met during embryogenesis and repair processes. It induces angiogenesis, promoting endothelial cell migration and capillary-tube formation in vivo. Co-expression of HGF/SF and c-Met receptor results in enhanced tumour growth, invasiveness and a mesenchymal-epithelial transition in some experimental tumours. Since mesothelioma cells have been reported to express c-Met receptor and to migrate in response to HGF/SF, we investigated human malignant pleural mesotheliomas for the demonstration of possible co-expression of the growth factor and its receptor. The microvessel density of the tumours was also analysed in order to assess the influence of HGF/SF expression on tumour angiogenesis. Thirty-nine paraffin-embedded specimens of malignant pleural mesotheliomas were immunostained by anti-HGF/SF and anti-c-Met antibodies and semiquantitatively evaluated. c-Met mRNA expression was visualised in ten tumour samples by a fluorescent in situ hybridisation method. Microvessel density was calculated by counting microvessels with a high-power field (200x) on von-Willebrand-factor-stained slides. We found an increased production of HGF/SF in 33/39 tumours and a corresponding overexpression of c-Met receptor in 29/39 specimens. The FISH method detected increased transcription of c-Met mRNA in malignant cells and in neighbouring vascular endothelial cells. HGF/SF-positive mesotheliomas had significantly higher microvessel densities compared to their HGF/SF-negative counterparts. The observed co-expression of HGF/SF and c-Met in malignant pleural mesotheliomas suggests a possible self-stimulation (autocrine loop) of tumour cells. On the basis of the significantly higher microvessel density values of malignant mesotheliomas overexpressing HGF/SF, we postulate, that HGF/SF may be an additional relevant factor in tumour angiogenesis in malignant pleural mesotheliomas.
Department of Pulmonology, Semmelweis Medical School, Budapest, Hungary.
E
E
Tolnay
C
C
Kuhnen
T
T
Wiethege
J E
JE
König
B
B
Voss
K M
KM
Müller
D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008654:Mesothelioma / Q000098:blood supply* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010997:Pleural Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000502:physiology*
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met