Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma

Our plain-English summary of Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma, by E. Tolnay, C. Kuhnen, T. Wiethege, et al (Journal of Cancer Research and Clinical Oncology, 1998).

The study

• Authors: E. Tolnay, C. Kuhnen, T. Wiethege, J.E. König, B. Voss, K.M. Müller
• Journal: Journal of Cancer Research and Clinical Oncology
• Published: 1998;124(6):291-6
• Cited by: 86 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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 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.

In plain English

This was a laboratory study of stored tumour tissue. The authors examined 39 archival samples of malignant pleural mesothelioma (14 epithelial, 17 biphasic, 8 sarcomatous). They used staining to look for a growth factor called hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, tested ten samples for c-Met messenger RNA, and counted small blood vessels in the tumours. The study did not examine asbestos exposure. HGF/SF was found in 33 of 39 tumours (85%) and c-Met in 29 of 39. Sarcomatous tumours stained more faintly for HGF/SF than epithelial tumours, and higher HGF/SF went with higher c-Met. Tumours with more HGF/SF had a statistically significantly higher density of small blood vessels. c-Met showed no such link. Epithelial tumours tended to have more vessels than sarcomatous ones, but this was not statistically significant. The authors concluded that the two molecules may form a self-stimulating (autocrine) loop in tumour cells. They suggested HGF/SF may play a role in blood vessel growth in these tumours, but cautioned that they had not measured another vessel-growth factor, VEGF.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory pathology study of archival tumour tissue (immunostaining, fluorescent in situ hybridisation, and microvessel counting)
• Who was studied: 39 archival tissue samples of malignant pleural mesothelioma: 14 epithelial, 17 biphasic and 8 sarcomatous; 10 of these were also analysed by fluorescent in situ hybridisation. The source and dates of the samples are not stated.
• Exposure: Asbestos exposure was not studied. The study measured HGF/SF and c-Met expression in tumour tissue and microvessel density.
• Main results:
  • 33 of 39 tumours (85%) stained positive for HGF/SF
  • 29 of 39 tumours (74%) stained positive for c-Met
  • Sarcomatous tumours stained more faintly for HGF/SF than epithelial tumours (P value printed as 0.00007). No similar relationship was found for c-Met (P value printed as 0.8232).
  • Increased HGF expression was associated with overexpression of c-Met, which was statistically significant (P value printed as 0.000254)
  • In the 10 tumours analysed by fluorescent in situ hybridisation, epithelial tumour cells contained high levels of c-Met mRNA and sarcomatous cells markedly lower levels
  • Median microvessel density was 19.5 microvessels per mm2 (minimum 0.02, maximum 54.7). Medians by subtype were 20.01 (epithelial), 18.74 (biphasic) and 5.8 (sarcomatous). The epithelial-versus-sarcomatous difference was not statistically significant (P value printed as 0.0549).
  • Increased HGF expression was associated with higher microvessel density, which was statistically significant (P value printed as 0.0323)
  • c-Met expression and microvessel density were apparently not related (P value printed as 0.7972)
• The authors' conclusion: The authors concluded that the HGF/SF and c-Met system probably represents a novel self-stimulating (autocrine) loop in malignant mesothelioma cells. They also suggested HGF/SF may be relevant to tumour blood vessel growth.
• Limitations the authors state:
  • The authors stated that conclusions about blood vessel growth should be drawn with caution, because they did not examine vascular endothelial growth factor (VEGF) expression

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Angiogenesis, Mesothelioma, High-Power Field, Fluorescence In Situ Hybridization (FISH), Malignant Mesothelioma.

Related studies

• Hepatocyte growth factor/scatter factor enhances the invasion of mesothelioma cell lines and the expression of matrix metalloproteinases — P. Harvey, I.M. Clark, et al. (2000)
• Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors — I.Y. Adamson, J. Bakowska, et al. (2000)
• The role of the HGF/Met axis in mesothelioma — T. Thayaparan, J.F. Spicer, et al. (2016)
• A₃ receptors are overexpressed in pleura from patients with mesothelioma and reduce cell growth via Akt/nuclear factor-κB pathway — K. Varani, S. Maniero, et al. (2011)
• KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos — I.Y. Adamson, J. Bakowska (2001)
• Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers — J.C. Pache, Y.M. Janssen, et al. (1998)

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