Autocrine stimulation of a human lung mesothelioma cell line is mediated through the transforming growth factor alpha/epidermal growth factor receptor mitogenic pathway

Our plain-English summary of Autocrine stimulation of a human lung mesothelioma cell line is mediated through the transforming growth factor alpha/epidermal growth factor receptor mitogenic pathway, by I.A. Mórocz, D. Schmitter, B. Lauber, et al (British Journal of Cancer, 1994).

The study

• Authors: I.A. Mórocz, D. Schmitter, B. Lauber, R.A. Stahel
• Journal: British Journal of Cancer
• Published: 1994;70(5):850-6
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant cells frequently acquire a certain independency of exogenous growth factors via the coexpression of epidermal growth factor receptor (EGFR) and epidermal growth factor (EGF)-related molecules. In the present study we investigate a possible involvement of EGF-related molecules in the growth of human lung mesothelioma. Four well-characterised cell lines are analysed for their responsiveness to exogenous EGF and transforming growth factor alpha (TGF-alpha) as well as for coexpression of EGFR and EGF/TGF-alpha. Both growth factors are able to stimulate DNA synthesis in three cell lines, although the degree of responsiveness is very variable, but neither EGF nor TGF-alpha has an effect on the cell line ZL34. In contrast, no heterogeneity is observed in the expression of EGFR, which is similarly high in all cell lines. Analysis of cell supernatants reveals that, whereas no EGF is detected, TGF-alpha is released by two cell lines. Furthermore, these two cell lines, ZL5 and ZL34, are shown to express the membrane anchored precursor pro-TGF-alpha. Thus, coexpression of EGFR and TGF-alpha is observed on two mesothelioma cell lines. The potential autocrine mitogenic role of TGF-alpha in these two cell lines was tested using neutralising antibodies against TGF-alpha and EGFR. In ZL5 cells DNA synthesis was not affected by the presence of neutralising antibodies, indicating that an external autocrine mitogenic pathway is not active in these cells. In ZL34 cells, however, the potential autocrine loop could be disrupted, as DNA synthesis was significantly reduced in the presence of neutralising antibodies. This result gives strong evidence for an autocrine role of TGF-alpha in the growth of the mesothelioma cell line ZL34.

In plain English

This laboratory study used four human pleural mesothelioma cell lines (ZL5, ZL34, ZL55 and SPC212), grown from previously untreated patients. It asked whether two growth signals, epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha), and their shared receptor (EGFR) drive the cells' growth. The study did not examine asbestos exposure. Added EGF or TGF-alpha increased DNA synthesis in three lines, but not in ZL34. All four lines carried large amounts of EGFR, and ZL34 had the most. No EGF was detected in the fluid collected from any of the lines. ZL34 released TGF-alpha at 7-15 pg per ml, ZL5 released trace amounts, and only these two lines carried the precursor form of TGF-alpha on their surface. Antibodies that block TGF-alpha or EGFR did not change DNA synthesis in ZL5. In ZL34 they lowered it significantly (P less than 0.01), but only partly. The authors concluded that this gives strong evidence that ZL34 cells stimulate their own growth through TGF-alpha. They noted that EGFR-bearing tumour samples might have been selected when the cell lines were established.

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
• Who was studied: Four human pleural mesothelioma cell lines (ZL5, ZL34, ZL55, SPC212) established from previously untreated patients, studied at University Hospital Zurich, Switzerland. Two control cell lines were used: NCI-H69 (EGFR-negative) and A431 (EGFR overexpression).
• Exposure: No asbestos or fiber exposure was studied. The cells were treated with added EGF and TGF-alpha, and with neutralising antibodies against TGF-alpha and EGFR, compared with a non-specific control antibody (MOPC21).
• Main results:
  • Added EGF or TGF-alpha increased DNA synthesis in three of the four cell lines. ZL5 and SPC212 were highly sensitive.
  • ZL55 was less sensitive, but showed a significant stimulatory effect (P < 0.01) at 10 ng per ml of TGF-alpha or EGF.
  • ZL34 showed no increase in DNA synthesis with EGF or TGF-alpha.
  • All four mesothelioma cell lines highly expressed EGFR on their surface. ZL34 had the largest amount, though less than the A431 control cells.
  • No EGF was detected in the conditioned media of any of the four lines.
  • ZL34 released TGF-alpha at 7-15 pg per ml (about 10-20 pg per million cells). ZL5 released unquantifiable trace amounts. ZL55 and SPC212 did not release TGF-alpha.
  • Only ZL5 and ZL34 expressed the membrane-anchored precursor pro-TGF-alpha, with a stronger signal on ZL34.
  • In ZL5, neutralising antibodies against TGF-alpha or EGFR did not affect DNA synthesis.
  • In ZL34, both neutralising antibodies produced a significant (P < 0.01) decrease in DNA synthesis compared with the non-specific control antibody. The reduction was only partial.
• The authors' conclusion: The authors concluded that the results give strong evidence for an autocrine role of TGF-alpha (cells stimulating their own growth) in the mesothelioma cell line ZL34. For ZL5, they concluded that at least one other mechanism is involved.
• Limitations the authors state:
  • The authors could not exclude that EGFR-bearing tumour samples were selected when the cell lines were established.
  • The authors stated that the reason the antibodies failed to block proliferation in ZL5 is not yet clear.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, EGFR.

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