Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology

Our plain-English summary of Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology, by P. Harvey, A. Warn, S. Dobbin, et al (British Journal of Cancer, 1998).

The study

• Authors: P. Harvey, A. Warn, S. Dobbin, N. Arakaki, Y. Daikuhara, M.C. Jaurand, R.M. Warn
• Journal: British Journal of Cancer
• Published: 1998;77(7):1052-9
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The expression of hepatocyte growth factor/scatter factor (HGF/SF) was studied in 12 mesothelioma cell lines characterized by either an epithelioid or a fibroblast-like phenotype. Conditioned media from these lines were analysed by bioassay and ELISA, and HGF/SF was detected in three cell lines, all with a fibroblast-like or mixed morphology. None of eight epithelioid cell lines expressed the factor. Thus, for these cell lines, the ability to secrete HGF/SF correlated with the cell phenotype. Following on from these observations, two cell lines, BR and BT, with a fibroblast-like and an epithelioid phenotype, respectively, were further investigated. Both cell lines expressed the Met receptor but only BR secreted HGF/SF. Both cell lines responded to exogenous HGF/SF treatment by a change of morphology but in different ways: BR became more elongated and bipolar, while BT formed more spread-out cell colonies. HGF/SF acted as a paracrine effector on the epithelioid BT cells and stimulated both cell-spreading and proliferation. Interestingly, BT cells spread but did not scatter in response to exogenous HGF/SF. In contrast BR cells showed only some stimulation of cell motility with HGF/SF and no increase in cell proliferation was observed. Because HGF/SF was previously found in the pleural effusion fluids of patients with malignant mesothelioma and in paraffin-embedded tumour tissues, it is concluded that HGF/SF may well stimulate the growth and spread of malignant mesothelioma in vivo by paracrine and/or autocrine mechanisms.

In plain English

This was a laboratory study of 12 cell lines grown from patients with malignant mesothelioma. It did not examine asbestos exposure. The authors tested whether the cells released a protein called hepatocyte growth factor/scatter factor (HGF/SF). Three of the 12 lines released it, and all three had a fibroblast-like or mixed cell shape. None of the eight lines with an epithelioid shape released it, and one fibroblast-like line also did not. Two lines were studied further: BR, which was fibroblast-like and released HGF/SF, and BT, which was epithelioid and did not. Both lines carried Met, the receptor for HGF/SF, and adding HGF/SF activated it. Added HGF/SF made BT cells spread out as connected sheets rather than scatter. It also raised BT cell growth by about 35% within 24 hours, but only when serum was present. BR cells moved somewhat more, but their growth did not change. The authors concluded that HGF/SF is probably involved in the development of malignant mesothelioma. They noted that the epithelioid lines might have stopped making HGF/SF in the laboratory.

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 study of human mesothelioma cell lines grown in culture (in vitro experiments)
• Who was studied: 12 human cell lines obtained from patients with malignant mesothelioma, taken from pleural effusion or from pleural aspirate or resected tumour material. Two lines, BR (fibroblast-like) and BT (epithelioid), were studied in detail.
• Exposure: No asbestos exposure was studied. The cells were treated with human recombinant HGF/SF at 10 ng/ml, for 24 hours in the motility and proliferation tests and for 10 to 20 minutes in the receptor activation test.
• Main results:
  • 3 of the 12 cell lines secreted HGF/SF. These were 3 of the 4 lines with a fibroblast-like or mixed morphology. None of the 8 epithelioid lines secreted it.
  • The fourth fibroblast-like cell line (line H) did not secrete HGF/SF by either test.
  • Measured HGF/SF levels in the three positive lines were 1 ng/ml (BR), 0.2 ng/ml (TA) and 2.0 ng/ml (D), as given in Table 1.
  • Both BR and BT made the genetic message (mRNA) for the Met receptor. Only BR made the message for HGF/SF.
  • In both BR and BT, adding HGF/SF increased activation (tyrosine phosphorylation) of the Met receptor at 10 minutes, and further at 20 minutes.
  • In BT (epithelioid) cells, HGF/SF increased cell spreading at the edges of scratch wounds but did not cause the cells to scatter. The cells moved as connected sheets.
  • In BR (fibroblast-like) cells, HGF/SF increased movement into scratch wounds. These motility effects were seen in cells grown in 10% serum, and the effect was much reduced in serum-free medium.
  • HGF/SF significantly increased BT cell proliferation by about 35% within 24 hours, but only in the presence of serum. BR cell proliferation showed no overall change.
• The authors' conclusion: The authors concluded that HGF/SF is probably involved in the development of malignant mesothelioma. They also concluded that the cells' ability to make HGF/SF, and their response to it, matched cell morphology.
• Limitations the authors state:
  • The epithelioid cell lines may have stopped making HGF/SF in culture, and might make it in the body.
  • Whether HGF/SF secretion is associated with the sarcomatoid form of mesothelioma has not yet been determined.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Epithelioid, Fibroblast, Pleural Effusion.

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)
• Effects of selected deubiquitinating enzyme inhibitors on the proliferation and motility of lung cancer and mesothelioma cell lines — T. Mirzapoiazova, A. Pozhitkov, et al. (2020)
• 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, C. Kuhnen, et al. (1998)
• The role of the HGF/Met axis in mesothelioma — T. Thayaparan, J.F. Spicer, et al. (2016)
• Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors — I.Y. Adamson, J. Bakowska, et al. (2000)
• Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells — K. Kawaguchi, H. Murakami, et al. (2009)

Browse more research in British Journal of Cancer, or return to medical research.