PMID- 9692834
OWN - NLM
STAT- MEDLINE
DCOM- 19980817
LR  - 20210102
IS  - 0171-5216 (Print)
IS  - 0171-5216 (Linking)
VI  - 124
IP  - 6
DP  - 1998
TI  - Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed 
      and associated with an increased microvessel density in malignant pleural 
      mesothelioma.
PG  - 291-6
AB  - 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.
FAU - Tolnay, E
AU  - Tolnay E
AD  - Department of Pulmonology, Semmelweis Medical School, Budapest, Hungary.
FAU - Kuhnen, C
AU  - Kuhnen C
FAU - Wiethege, T
AU  - Wiethege T
FAU - Konig, J E
AU  - Konig JE
FAU - Voss, B
AU  - Voss B
FAU - Muller, K M
AU  - Muller KM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Hepatocyte Growth Factor/biosynthesis/*physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Mesothelioma/*blood supply/*metabolism
MH  - Neovascularization, Pathologic/metabolism
MH  - Pleural Neoplasms/*blood supply/*metabolism
MH  - Proto-Oncogene Proteins c-met/biosynthesis/*physiology
EDAT- 1998/08/06 00:00
MHDA- 1998/08/06 00:01
CRDT- 1998/08/06 00:00
PHST- 1998/08/06 00:00 [pubmed]
PHST- 1998/08/06 00:01 [medline]
PHST- 1998/08/06 00:00 [entrez]
AID - 10.1007/s004320050171 [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 1998;124(6):291-6. doi: 10.1007/s004320050171.