Molecular Mechanism for the Induction of Mesothelioma by Asbestos

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Biophysical Journal

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Biophysics | Cancer Biology | Cell Biology | Molecular Biology


Mesothelioma is an incurable form of cancer located in the pleural lining around the lungs. It is associated almost exclusive with the inhalation of mineral fibers called asbestos. Despite the well-known association between asbestos and mesothelioma, little is know about the mechanism of induction. The binding of asbestos to epidermal growth factor receptor (EGFR), a transmembrane signal protein, has been proposed as a trigger switch for downstream signaling of kinases and expression of genes associated with cancer. Here we used atomic force microscopy (AFM) to investigate the binding of the extracellular domain of EGFR to two minerals, crocidolite versus riebeckite in buffer solution. Crocidolite [Na2(Fe,Mg)5Si8O22(OH)2] is the asbestiform mineral most commonly associated with human mesothelioma. Riebeckite is chemically equivalent to crocidolite but has a non-asbestiform, fragmental habit, and it is not associated with cancer. AFM measurements revealed an attractive force between EGFR and each mineral. The rupture force of the mineral-EGFR bond increased with increasing loading rates. The correlation between rupture force and loading rate was stronger for crocidolite-EGFR than riebeckite-EGFR. The Bell model was used to estimate the bond lifetime for both mineral-protein pairs. The lifetime for the EGFR bond was roughly three times shorter for crocidolite than riebeckite. The fast but repeatable binding of EGFR with crocidolite fibers, which persist in the lungs for a period longer than a human's lifespan, may continually trigger the activation switch leading to chronic expression of genes involved in asbestos-related cancers.


Abstract of poster presentation.


Elsevier Science