Effect of insulin and epidermal growth factors on the synthesis of glycosaminoglycans/proteoglycans in cultured human malignant mesothelioma cells of different phenotypic morphology

Our plain-English summary of Effect of insulin and epidermal growth factors on the synthesis of glycosaminoglycans/proteoglycans in cultured human malignant mesothelioma cells of different phenotypic morphology, by G.N. Tzanakakis, N.K. Karamanos, A. Syrokou, et al (APMIS, 1996).

The study

• Authors: G.N. Tzanakakis, N.K. Karamanos, A. Syrokou, A. Hjerpe
• Journal: APMIS
• Published: 1996;104(10):718-28
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Two human malignant mesothelioma cell sublines, one with a fibroblast-like and the other with an epithelial differentiation, were examined for their capacity to synthesize glycosaminoglycans in the presence of IGF-I, EGF, and their combination. This synthesis depends on the morphology of the mesothelioma cells, with many-fold higher amounts of both hyaluronan and proteoglycans being produced by the cells with epithelial morphology than by those of the fibroblast phenotype. In both cell lines this synthesis was affected in a dose-dependent fashion by the exogenously added growth factors and exposure to IGF-I and EGF in combination showed a synergistic effect. This effect of those factors seems to be mediated via protein tyrosin kinase-dependent receptors and was different in the fibroblast-like and epithelial cells. The synthetic rates of the various glycosaminoglycans formed (hyaluronan, galactosaminoglycans and heparan sulfate) were also variously affected by these factors, indicating differences in how the synthesis of the various glycosaminoglycans is regulated. The results obtained suggest a close correlation between the presence of the appropriate growth factor(s), the process of cell differentiation and the synthesis of glycosaminoglycans in these cells.

In plain English

This was a laboratory study of two cell lines grown from one human malignant pleural mesothelioma. STAV-FCS had a fibroblast-like growth pattern, and STAV-AB had a predominantly epithelial morphology. The study did not examine asbestos exposure. The authors added two growth factors, insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF), alone and together. They then measured how much the cells made of a group of molecules called glycosaminoglycans: hyaluronan, chondroitin sulphate and heparan sulphate. Without added factors, total glycosaminoglycan amounts in STAV-AB were 6-8-fold higher than in STAV-FCS. In STAV-FCS, IGF-I at 100 ng/ml gave a 2-fold rise in hyaluronan, and EGF at 100 ng/ml gave a more than 5-fold rise. The two together raised hyaluronan 6.8-9.5 times. In STAV-AB, IGF-I doubled hyaluronan and chondroitin sulphate, and the combination raised hyaluronan 4.5- to 5-fold. Genistein, which blocks protein tyrosine kinase signalling, completely abolished the stimulation in both cell lines. The authors concluded that the results suggest a close correlation between growth factors, cell differentiation and glycosaminoglycan synthesis in these cells.

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 cultured human malignant mesothelioma cell lines
• Who was studied: Two cell sublines, STAV-FCS (fibroblast-like phenotype) and STAV-AB (epithelial morphology), established from a malignant pleural mesothelioma and used between passages 50 and 70. The work was done at Karolinska Institute, Huddinge, Sweden, and University of Patras, Greece
• Exposure: No asbestos exposure was studied. Cells were exposed to the growth factors IGF-I (1, 10, 20, 65 and 100 ng/ml) and EGF (5, 10, 20 and 100 ng/ml), alone or combined. Some cultures were pre-treated with genistein, a protein tyrosine kinase blocker
• Main results:
  • Both sublines produced hyaluronan, galactosaminoglycans and heparan sulphate; chondroitin sulphate was the only galactosaminoglycan produced
  • Without added growth factors, total glycosaminoglycan amounts in the epithelial STAV-AB subline were 6-8-fold higher than in the fibroblast-like STAV-FCS subline
  • Most hyaluronan (94%) was recovered in the culture medium
  • In STAV-FCS, IGF-I caused a 2-fold increase in hyaluronan synthesis at 100 ng/ml and had no effect on heparan sulphate synthesis
  • In STAV-FCS, EGF at 100 ng/ml increased hyaluronan synthesis more than 5-fold and increased chondroitin sulphate and heparan sulphate production 1.8- and 1.5-fold, respectively
  • In STAV-FCS, IGF-I and EGF combined increased hyaluronan synthesis 6.8-9.5 times, an effect the authors described as seeming to be synergistic
  • In STAV-AB, IGF-I at 100 ng/ml increased synthesis of both hyaluronan and chondroitin sulphate 2-fold, and EGF had a stronger effect on hyaluronan secretion (3.5-fold)
  • In STAV-AB, the combination increased hyaluronan production 4.5- to 5-fold compared with cultures without added factors
  • Pre-treatment with genistein completely abolished the stimulation by IGF-I and EGF in both sublines. In unstimulated control cells, residual formation of the various glycosaminoglycans was 10-50% of untreated cells
• The authors' conclusion: The authors concluded that the results suggest a close correlation between the presence of the appropriate growth factor(s), the process of cell differentiation and glycosaminoglycan synthesis in these cells. They also suggested that large amounts of hyaluronan in mesothelioma effusions may be associated with autocrine mechanisms like those regulating tumour growth

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Fibroblast, Mesothelioma, Synergistic Effect.

Related studies

• Proteoglycans in human malignant mesothelioma. Stimulation of their synthesis induced by epidermal, insulin and platelet-derived growth factors involves receptors with tyrosine kinase activity — A. Syrokou, G.N. Tzanakakis, et al. (1999)
• Glycosaminoglycans from two human malignant mesothelioma cell lines: determination, distribution, and effect of platelet-derived growth factor on their synthesis — G.N. Tzanakakis, N.K. Karamanos, et al. (1995)
• Different accumulation of activated extracellular signal-regulated kinases (ERK 1/2) and role in cell-cycle alterations by epidermal growth factor, hydrogen peroxide, or asbestos in pulmonary epithelial cells — S. Buder-Hoffmann, C. Palmer, et al. (2001)
• Role of peptide growth factors in asbestos-related human lung cancer — B. Guillemin, Y. Zhang, et al. (1991)
• Expression of genes coding for proteoglycans and Wilms' tumour susceptibility gene 1 (WT1) by variously differentiated benign human mesothelial cells — M. Gulyás, K. Dobra, et al. (1999)
• Solitary fibrous tumor of the pleura. An immunohistochemical, electron microscopic and tissue culture study of a tumor producing insulin-like growth factor I in a patient with hypoglycemia — E.H. Strøm, F. Skjørten, et al. (1991)

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