Repetitive dissociation from crocidolite asbestos acts as persistent signal for epidermal growth factor receptor

Our plain-English summary of Repetitive dissociation from crocidolite asbestos acts as persistent signal for epidermal growth factor receptor, by E.S. Taylor, A.G. Wylie, B.T. Mossman, et al (Langmuir, 2013).

The study

• Authors: E.S. Taylor, A.G. Wylie, B.T. Mossman, S.K. Lower
• Journal: Langmuir
• Published: 2013;29(21):6323-30
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma is an incurable form of cancer located most commonly in the pleural lining of the lungs and is associated almost exclusively with the inhalation of asbestos. The binding of asbestos to epidermal growth factor receptor (EGFR), a transmembrane signal protein, has been proposed as a trigger for downstream signaling of kinases and expression of genes involved in cell proliferation and inhibition of apoptosis. Here, we investigate the molecular binding of EGFR to crocidolite (blue asbestos; Na2(Fe(2+),Mg)3Fe2(3+)Si8O22(OH)2) in buffer solution. Atomic force microscopy measurements revealed an attractive force of interaction (i.e., bond) as EGFR was pulled from contact with long fibers of crocidolite. The rupture force of this bond increased with loading rate. According to the Bell model, the off-rate of bond dissociation (k(off)) for EGFR was 22 s(-1). Similar experiments with riebeckite crystals, the nonasbestiform variety of crocidolite, yielded a k(off) of 8 s(-1). These k(off) values on crocidolite and riebeckite are very rapid compared to published values for natural agonists of EGFR like transforming growth factor and epidermal growth factor. This suggests binding of EGFR to the surfaces of these minerals could elicit a response that is more potent than biological hormone or cytokine ligands. Signal transduction may cease for endogenous ligands due to endocytosis and subsequent degradation, and even riebeckite particles can be cleared from the lungs due to their short, equant habit. However, the fibrous habit of crocidolite leads to lifelong persistence in the lungs where aberrant, repetitious binding with EGFR may continually trigger the activation switch leading to chronic expression of genes involved in oncogenesis.

In plain English

In laboratory tests, the authors used atomic force microscopy to measure how EGFR, a receptor protein from human cancer cells, bound to and separated from crocidolite (blue asbestos) fibers and riebeckite, the non-fibrous form of the same mineral. They collected more than 10 000 measurements in buffered saline; no people, animals or living cells were tested. EGFR bound in 37% of contacts with crocidolite, versus 18% for riebeckite and for glass. The calculated rate at which the bond broke was 22 per second for crocidolite (95% confidence interval 7 to 40) and 8 per second for riebeckite (interval less than 1 to 32). The difference between the minerals was not statistically significant. Both rates were faster than values other studies published for the body's natural substances that bind EGFR. The authors concluded that crocidolite fibers, which they described as persisting in the lung, pleura or peritoneum, would act as persistent triggers for proteins like EGFR. They noted three limits: they tested extracted EGFR rather than EGFR in cells, they examined only mineral growth surfaces, and they studied only one of six asbestos minerals.

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 experiment (atomic force microscopy force measurements analysed with the Bell model) on an extracted protein and mineral samples
• Who was studied: EGFR protein from human carcinoma A431 cells (commercial), tested against crocidolite fibers from the National Institute of Environmental Health Sciences, riebeckite crystals from a private collector (Papineau, Quebec), and glass as a control; more than 10 000 force curves
• Exposure: Contact of EGFR with crocidolite (asbestiform riebeckite) fibers compared with nonasbestiform riebeckite crystals of the same mineral composition; only natural growth surfaces were tested, not crushed or ground material
• Main results:
  • EGFR binding events occurred in 37% of contacts with crocidolite, versus 18% with riebeckite and 18% with glass (p = 0.001 for each comparison with crocidolite, Table 1)
  • For crocidolite, the off-rate of bond dissociation (koff) was 22 per second (95% CI 7 to 40), corresponding to a bond lifetime of about 45 ms
  • For nonasbestiform riebeckite, koff was 8 per second (95% CI less than 1 to 32)
  • The apparent difference in koff between crocidolite and riebeckite was not statistically significant (p greater than 0.05)
  • In a control experiment, coating the EGFR tip with an anti-EGFR antibody increased, rather than decreased, binding to crocidolite, from 37% to 57%; the authors attributed this to the antibody itself sticking to crocidolite
  • The koff values for both minerals were faster than published values from other studies for EGFR binding to its natural ligands EGF (0.002 to 0.75 per second) and TGF alpha (0.04 to 2.3 per second)
• The authors' conclusion: The authors concluded that crocidolite fibers, which they described as persisting in the lung, pleura or peritoneum, will act as persistent triggers for signaling proteins like EGFR over the long latency periods of asbestos-related cancers
• Limitations the authors state:
  • Only mineral growth surfaces were examined; cleavage or breakage fragments, which may occur in work-related exposure to riebeckite, may react differently
  • Extracted EGFR was used rather than EGFR in its natural state in a cell membrane
  • Only one of the six asbestos minerals was studied

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Mesothelioma, EGFR, Apoptosis, Riebeckite, Non-Asbestiform, Cytokine, Habit.

Related studies

• 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 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)
• Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma — J. Kurai, H. Chikumi, et al. (2012)
• Patients with peritoneal mesothelioma lack epidermal growth factor receptor tyrosine kinase mutations that would make them sensitive to tyrosine kinase inhibitors — N. Kalra, A. Ashai, et al. (2012)
• Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers — J.C. Pache, Y.M. Janssen, et al. (1998)

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