Glycosaminoglycans from two human malignant mesothelioma cell lines: determination, distribution, and effect of platelet-derived growth factor on their synthesis

Our plain-English summary of Glycosaminoglycans from two human malignant mesothelioma cell lines: determination, distribution, and effect of platelet-derived growth factor on their synthesis, by G.N. Tzanakakis, N.K. Karamanos, J. Klominek, et al (Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire, 1995).

The study

• Authors: G.N. Tzanakakis, N.K. Karamanos, J. Klominek, A. Hjerpe
• Journal: Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire
• Published: 1995;73(1-2):59-66
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The synthesis and distribution of glycosaminoglycans (GAGs) were studied in two human malignant mesothelioma cell lines: one with fibroblast-like morphology and the other with epithelial differentiation. Analyses using highly sensitive high-pressure liquid chromatography techniques and agarose gel electrophoresis showed that these cells produce not only hyaluronan (HA) but also galactosaminoglycans (GalAGs, chondroitin sulfate and (or) dermatan sulfate) and heparan sulfate (HS). In both cell lines most of the HA (87-90%) and GalAGs (57-66%) are secreted into the extracellular matrix. Although HS is mainly bound to the cell surface in fibroblast-differentiated cells (75%), in epithelial type cells only 40% occurs in the cell-associated fraction. The amounts of secreted GAGs are 6- to 8-fold higher in epithelial than in fibroblast-like mesothelioma cultures. In cells with the fibroblast phenotype, the beta-homodimer of platelet-derived growth factor (PDGF) in a concentration of 1.5 ng/mL stimulates HA and GalAG synthesis 5-fold and that of HS 10-fold, whereas higher concentrations suppress this stimulatory effect. The stimulatory effect, observed at low concentrations of this growth factor, was completely blocked by the addition of antibodies against this factor. In epithelially differentiated cells, the production of all GAGs was suppressed after addition of this factor, even at low concentrations. We therefore suggest that mesothelioma cells can produce GAGs, the synthesis of which is dependent on the presence and concentration of PDGF beta-homodimer. The differences between the two cell lines regarding the effect of this growth factor on GAG synthesis indicates that the regulation of this synthesis is complex, other factors also being important.

In plain English

This laboratory study examined two cell lines, STAV-FCS and STAV-AB, grown from the fluid around the lung (pleural effusion) of a malignant pleural mesothelioma. In fetal calf serum the cells looked like fibroblasts. In human AB serum they looked epithelial. The authors measured substances the cells made, called glycosaminoglycans: hyaluronan, galactosaminoglycans and heparan sulfate. They also tested a growth factor, PDGF-BB, and antibodies against it. Both lines released most of their hyaluronan (87 and 90%) into the culture medium. The epithelial-type cells secreted 8-fold more hyaluronan and galactosaminoglycans, and 6-fold more heparan sulfate, than the fibroblast-like cells. Adding 1.5 ng/mL PDGF-BB raised secretion by the fibroblast-like cells 5- to 7-fold for hyaluronan and galactosaminoglycans and 15-fold for heparan sulfate. At 12 ng/mL or more, that effect faded. In the epithelial-type cells, PDGF-BB reduced production. The authors concluded that PDGF-BB may take part in regulating this production but that the regulation is complex. The article describes no asbestos exposure, and some numbers in its abstract differ from its results.

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 (in vitro) study of human mesothelioma cell lines in culture
• Who was studied: Two human mesothelioma cell sublines, STAV-FCS (fibroblast-like, grown in fetal calf serum) and STAV-AB (epithelial, grown in human AB serum), established from the effusion of a malignant pleural mesothelioma
• Exposure: No asbestos exposure was studied. The cells were treated with the growth factor PDGF-BB at 0, 1.5, 8 and 12 ng/mL, or with anti-PDGF-BB antibody at 80 ng/mL, and were grown in either fetal calf serum or human AB serum.
• Main results:
  • In both cell lines, most hyaluronan was secreted into the medium: 87% for the fibroblast-like line and 90% for the epithelial line.
  • Most galactosaminoglycans were secreted into the medium by both lines (57 and 66%).
  • Of the heparan sulfate, 25% was recovered in the medium of the fibroblast-like cells and 69% in the medium of the epithelial cells.
  • The epithelial STAV-AB cells secreted 8-fold more hyaluronan and galactosaminoglycans, and 6-fold more heparan sulfate, than the fibroblast-like STAV-FCS cells.
  • In fibroblast-like STAV-FCS cells, 1.5 ng/mL PDGF-BB increased secretion of hyaluronan and galactosaminoglycans 5- to 7-fold and of heparan sulfate 15-fold.
  • In fibroblast-like cells, at 12 ng/mL PDGF-BB or more, values were somewhat higher than, similar to, or even lower than controls.
  • In STAV-FCS cells, anti-PDGF-BB antibody reduced secretion of hyaluronan, galactosaminoglycans and heparan sulfate to 50, 62 and 30%, respectively.
  • In epithelial STAV-AB cells, PDGF-BB reduced the synthesis and secretion of all three glycosaminoglycans, with secreted hyaluronan decreasing by 50%.
  • In STAV-AB cells, anti-PDGF-BB produced partial inhibition of 35, 52 and 36% for hyaluronan, galactosaminoglycans and heparan sulfate, respectively.
• The authors' conclusion: The authors concluded that PDGF-BB may take part in regulating glycosaminoglycan synthesis in these mesothelioma cells, but that the regulation is complex and other factors may also be involved.
• Limitations the authors state:
  • The authors state that the nature of the proteoglycans carrying the cell-associated glycosaminoglycans remains to be clarified.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Platelet-Derived Growth Factor (PDGF), Fibroblast, Mesothelioma.

Related studies

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• Differential proliferation of rat lung fibroblasts induced by the platelet-derived growth factor-AA, -AB, and -BB isoforms secreted by rat alveolar macrophages — J.C. Bonner, A.R. Osornio-Vargas, et al. (1991)
• Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts — J.C. Bonner, A.L. Goodell, et al. (1993)
• Chrysotile asbestos stimulates platelet-derived growth factor-AA production by rat lung fibroblasts in vitro: evidence for an autocrine loop — J.A. Lasky, P.G. Coin, et al. (1995)

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