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, Cornelius Kuhnen, Thorsten Wiethege, Jens Eckehard König, Bruno Voss, Klaus Michael Müller

Research output: Contribution to journalArticle

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Abstract

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 coexpression 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.

Original languageEnglish
Pages (from-to)291-296
Number of pages6
JournalJournal of Cancer Research and Clinical Oncology
Volume124
Issue number6
DOIs
Publication statusPublished - 1998

Fingerprint

Proto-Oncogene Proteins c-met
Hepatocyte Growth Factor
Microvessels
Neoplasms
Malignant Mesothelioma
Mesothelioma
Cell Movement
Endothelial Cells

Keywords

  • Angiogenesis
  • Autocrine loop
  • C-Met receptor
  • HGF/SF
  • Malignant mesothelioma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hepatocyte growth factor/scatter factor and its receptor c-met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma. / Tolnay, E.; Kuhnen, Cornelius; Wiethege, Thorsten; König, Jens Eckehard; Voss, Bruno; Müller, Klaus Michael.

In: Journal of Cancer Research and Clinical Oncology, Vol. 124, No. 6, 1998, p. 291-296.

Research output: Contribution to journalArticle

Tolnay, E. ; Kuhnen, Cornelius ; Wiethege, Thorsten ; König, Jens Eckehard ; Voss, Bruno ; Müller, Klaus Michael. / Hepatocyte growth factor/scatter factor and its receptor c-met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma. In: Journal of Cancer Research and Clinical Oncology. 1998 ; Vol. 124, No. 6. pp. 291-296.
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