Upregulation of 9 genes, including that for thioredoxin, during epithelial differentiation of mesothelioma cells

Our plain-English summary of Upregulation of 9 genes, including that for thioredoxin, during epithelial differentiation of mesothelioma cells, by X. Sun, K. Dobra, M. Björnstedt, et al (Differentiation; Research in Biological Diversity, 2000).

The study

• Authors: X. Sun, K. Dobra, M. Björnstedt, A. Hjerpe
• Journal: Differentiation; Research in Biological Diversity
• Published: 2000;66(4-5):181-8
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is a tumour originating from mesothelial cells, and it exhibits epithelial, fibrous, or biphasic differentiation. This tumour is highly resistant to therapy, and presence of a sarcomatous growth pattern has been associated with worse prognosis. A mesothelioma cell line with retained ability to differentiate into either epithelial or fibroblast-like phenotype was subjected to subtractive hybridisation in order to identify the genes coupled to tumour cell differentiation. Nine genes were found to be selectively overexpressed in the epithelial sub-line, compared to only two genes in the fibroblast-like phenotype. This may support the idea that the sarcomatous phenotype represents a less differentiated tumour. One of the genes that is differentially expressed by the epithelial cells was thioredoxin, a small redox-active protein associated with cell-growth and differentiation. This overexpression was accompanied by increased protein levels both intracellularly and in the medium. Thioredoxin is reduced by the selenoprotein thioredoxin reductase and NADPH. The activity of this enzyme was high in both cell sub-lines but induced 2-fold in the epithelially-differentiated cells. Overexpression of thioredoxin might be a factor behind the poor prognosis and reduced responsiveness to therapy of mesotheliomas. Epithelial differentiation in this cell line has previously been linked to increased synthesis of heparan sulphate proteoglycans. The possible formation of complexes including thioredoxin, thioredoxin reductase, and heparan sulphate proteoglycans might play a role in the local control of cell growth and differentiation.

In plain English

This was a laboratory study of human malignant mesothelioma cells, not of people. The authors compared two sub-lines of one cell line (STAV), both from the same tumour. In human AB serum the cells grew with an epithelial shape (STAV-AB); in fetal calf serum, fibroblast-like (STAV-FCS). No asbestos exposure was studied. Using subtractive hybridisation, the authors searched for genes expressed more in one sub-line. Of 11 known genes found, nine were expressed more strongly in the epithelial sub-line, including thioredoxin, and two in the fibroblast-like sub-line. In 3 independent determinations, the epithelial sub-line's culture medium held 3.7 plus or minus 0.7 times more thioredoxin protein, and its cell extracts 2.4 plus or minus 0.9 times more, than the fibroblast-like sub-line's. Activity of the enzyme thioredoxin reductase was twice as high in the epithelial cells. The authors suggested that fibroblast-like mesothelioma cells may be less differentiated, which, if true, might partly explain the worse prognosis of tumours with a sarcomatous component. They noted that any link between thioredoxin and prognosis remains to be shown.

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 (cell culture) study comparing gene expression between two sub-lines of a mesothelioma cell line using subtractive hybridisation
• Who was studied: Two sub-lines of the STAV human malignant mesothelioma cell line, both from the same tumour: STAV-AB (grown in human AB serum, epithelial) and STAV-FCS (grown in fetal calf serum, fibroblast-like)
• Exposure: No asbestos or fiber exposure was studied. The condition compared was the serum used to grow the cells (fetal calf serum versus human AB serum), which determined their shape
• Main results:
  • Subtractive hybridisation revealed cDNAs corresponding to 11 previously known genes
  • Nine genes were selectively overexpressed in the epithelial STAV-AB sub-line and two in the fibroblast-like STAV-FCS sub-line. This was a comparison of expression levels, not proof that the genes were absent from the other sub-line: thioredoxin protein, for example, was measured in both.
  • Five of the epithelial-line clones matched ribosomal proteins L31, L35, S3, L7a and S17
  • After 2 days of culture, most thioredoxin protein had been secreted into the medium
  • Medium from the epithelial sub-line contained 3.7 plus or minus 0.7 times more thioredoxin than medium from the fibroblast-like culture, in 3 independent determinations. The article does not say what kind of spread the 0.7 represents.
  • Cell extracts of the epithelial sub-line showed a 2.4 plus or minus 0.9-fold increase in thioredoxin compared with the fibroblast-like sub-line, in 3 independent determinations
  • Thioredoxin reductase activity was twice as high in the epithelial STAV-AB cells as in the fibroblast-like STAV-FCS cells, averaged over 6 experiments
• The authors' conclusion: The authors concluded that fibroblast-like mesothelioma cells may be less differentiated than epithelial ones, which, if true, might partly explain why tumours with a sarcomatous component have a worse prognosis
• Limitations the authors state:
  • Other genes involved in differentiation may have been missed if their difference in expression was too small to overcome the 23-fold driver:tester ratio
  • Differential regulation of a gene does not prove that the gene plays a functional role
  • A link between thioredoxin overexpression and poor prognosis or therapy response in mesothelioma has not been shown
  • It cannot be excluded that fetal calf serum contains factors that down-regulate genes

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, Malignant Mesothelioma, Mesothelial Cells, Biphasic Mesothelioma, Prognosis, Fibroblast.

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