Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers

Our plain-English summary of Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers, by J.C. Pache, Y.M. Janssen, E.S. Walsh, et al (The American Journal of Pathology, 1998).

The study

• Authors: J.C. Pache, Y.M. Janssen, E.S. Walsh, T.R. Quinlan, C.L. Zanella, R.B. Low, D.J. Taatjes, B.T. Mossman
• Journal: The American Journal of Pathology
• Published: 1998;152(2):333-40
• Cited by: 80 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Epidermal growth factor (EGF) is a potent mitogen for human mesothelial cells, and autophosphorylation of the EGF receptor (EGF-R) occurs in these cell types after exposure to asbestos, a carcinogen associated with the development of mesothelioma. Here, the intensity and distribution of EGF-R protein was documented by immunocytochemistry in a human mesothelial cell line (MET5A) exposed to various concentrations of crocidolite asbestos and man-made vitreous fibers (MMVF-10). Whereas cells in contact with or phagocytizing shorter asbestos fibers (<60 microm length) or MMVF-10 at a range of concentrations showed no increase in EGF-R protein as determined by immunofluorescence, elongated cells phagocytizing and surrounding longer fibers (> or =60 microm) showed intense staining for EGF-R. In contrast, human A549 lung carcinoma cells showed neither elongation nor increased accumulation of EGF-R protein in response to long fibers. Patterns of aggregation and increases in EGF-R protein in mesothelial cells phagocytizing long asbestos fibers were distinct from diffuse staining of phosphotyrosine residues observed in asbestos-exposed cultures. These studies indicate that aggregation of EGF-R by long fibers may initiate cell signaling cascades important in asbestos-induced mitogenesis and carcinogenesis.

In plain English

This short laboratory report used human cells grown in dishes, not people. The authors exposed a human mesothelial cell line (MET5A) to crocidolite asbestos or to a man-made vitreous fiber (MMVF-10) for 2 hours, at 0.5 to 2.5 micrograms per square centimeter of dish. They used antibody staining and microscopy to look at the epidermal growth factor receptor (EGF-R), a cell-surface protein involved in growth signals. Most untreated cells showed faint EGF-R staining, though occasional dividing cells stained intensely. After crocidolite at 2.5 micrograms per square centimeter, cells surrounding fibers longer than 60 micrometers became elongated and stained very intensely. The number of these elongated, EGF-R-positive cells rose significantly with crocidolite but not with MMVF-10 at any concentration tested. Of about 100 elongated cells examined after crocidolite exposure, approximately 75% of the EGF-R-positive ones were touching long fibers. Asbestos also caused a diffuse increase in phosphotyrosine staining. A human lung cancer cell line (A549) showed no such EGF-R increase. The authors chose the 60-micrometer cutoff arbitrarily. They concluded that their results suggest a mechanism for the increased pathogenicity of long asbestos fibers in mesothelioma.

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) cell culture experiment, published as a short communication, using antibody staining with fluorescence and confocal microscopy and computer-assisted image analysis
• Who was studied: A human mesothelial cell line (MET5A), immortalized with SV-40 T antigen, compared with a human lung adenocarcinoma cell line (A549); work done at the University of Vermont College of Medicine
• Exposure: Reference samples of crocidolite asbestos and man-made vitreous fibers (MMVF-10), added to cultures at 0.5 to 2.5 micrograms per square centimeter of dish for 2 hours; control cultures received mock handling
• Main results:
  • Most untreated (control) MET5A cells showed faint, punctate EGF-R staining at the cell membrane
  • In untreated cultures, occasional dividing (mitotic) cells stained intensely for EGF-R
  • In MET5A cells exposed to crocidolite at 2.5 micrograms per square centimeter, cells surrounding fibers longer than 60 micrometers became elongated and showed very intense EGF-R staining
  • Total numbers of elongated, EGF-R-positive MET5A cells increased significantly after crocidolite at 2.5 micrograms per square centimeter, but not after MMVF-10 at any concentration evaluated
  • Of approximately 100 elongated MET5A cells evaluated after crocidolite exposure at 2.5 micrograms per square centimeter, approximately 75% of the elongated EGF-R-positive cells were in contact with long fibers (p less than 0.05). The remaining 25% were in contact with shorter fibers, which often clumped together inside the cell to resemble a long fiber
  • MET5A cells exposed to asbestos showed a diffuse but more striking staining of phosphotyrosine residues than untreated control cells
  • Human A549 lung cells exposed to crocidolite showed little reaction to or attempted engulfing of fibers, and no increased or localized EGF-R accumulation
• The authors' conclusion: The authors concluded that their results suggest a mechanism to explain the increased pathogenicity of long asbestos fibers in the development of mesothelioma
• Limitations the authors state:
  • The 60-micrometer cutoff between long and short fibers was chosen arbitrarily, because fibers of that size could be viewed whole in a single microscope field

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Mesothelioma, Crocidolite, Vitreous, Carcinoma, Carcinogenesis.

Related studies

• Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres — S.P. Faux, C.E. Houghton, et al. (2000)
• Role of iron in inactivation of epidermal growth factor receptor after asbestos treatment of human lung and pleural target cells — A. Baldys, A.E. Aust (2005)
• Asbestos-induced phosphorylation of epidermal growth factor receptor is linked to c-fos and apoptosis — C.L. Zanella, C.R. Timblin, et al. (1999)
• Increased serum concentrations of growth factor receptors and Neu in workers previously exposed to asbestos — N. Lahat, P. Froom, et al. (1999)
• Epidermal growth factor receptor mutations in 510 Finnish non--small-cell lung cancer patients — S. Mäki-Nevala, M. Rönty, et al. (2014)
• Repetitive dissociation from crocidolite asbestos acts as persistent signal for epidermal growth factor receptor — E.S. Taylor, A.G. Wylie, et al. (2013)

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