HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR AND ITS RECEPTOR C-MET ARE OVEREXPRESSED AND ASSOCIATED WITH AN INCREASED MICROVESSEL DENSITY IN MALIGNANT PLEURAL MESOTHELIOMA
E. Tolnay et al., HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR AND ITS RECEPTOR C-MET ARE OVEREXPRESSED AND ASSOCIATED WITH AN INCREASED MICROVESSEL DENSITY IN MALIGNANT PLEURAL MESOTHELIOMA, Journal of cancer research and clinical oncology, 124(6), 1998, pp. 291-296
Hepatocyte growth factor/scatter factor (HGF/SF) stimulates cell proli
feration, motility and invasiveness via its receptor c-Met during embr
yogenesis and repair processes. It induces angiogenesis, promoting end
othelial cell migration and capillary-tube formation in vivo. Go-expre
ssion of HGF/SF and c-Met receptor results in enhanced tumour growth,
invasiveness and a mesenchymal-epithelial transition in some experimen
tal tumours. Since mesothelioma cells have been reported to express c-
Met receptor and to migrate in response to HGF/SF, we investigated hum
an malignant pleural mesotheliomas for the demonstration of possible c
oexpression of the growth factor and its receptor. The microvessel den
sity of the tumours was also analysed in order to assess the influence
of HGF/SF expression on tumour angiogenesis. Thirty-nine paraffin-emb
edded specimens of malignant pleural mesotheliomas were immunostained
by anti-HGF/SF and anti-c-Met antibodies and semiquantitatively evalua
ted. c-Met mRNA expression was visualised in ten tumour samples by a f
luorescent in situ hybridisation method. Microvessel density was calcu
lated 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 re
ceptor in 29/39 specimens. The FISH method detected increased transcri
ption of c-Met mRNA in malignant cells and in neighbouring vascular en
dothelial cells. HGF/SF-positive mesotheliomas had significantly highe
r microvessel densities compared to their HGF/SF-negative counterparts
. The observed coexpression of HGF/SF and c-Met in malignant pleural m
esotheliomas suggests a possible self-stimulation (autocrine loop) of
tumour cells. On the basis of the significantly higher microvessel den
sity values of malignant mesotheliomas overexpressing HGF/SF, we postu
late, that HGF/SF may be an additional relevant factor in tumour angio
genesis in malignant pleural mesotheliomas.