Abstract
This is the first report of the use of laser ablation–inductively coupled plasma time-of-flight mass spectrometry (LA–ICP–TOFMS) to analyze human malignant pleural mesothelioma (MPM) samples at the cellular level. MPM is an aggressive, incurable cancer associated with asbestos exposure, with a long latency and poor overall survival. Following careful optimization of the laser fluence, the simultaneous ablation of soft biological tissue and hard mineral fibers was possible, allowing the spatial detection of elements such as Si, Mg, Ca, and Fe, which are also present in the glass substrate. A low-dispersion LA setup was employed, which provided the high spatial resolution necessary to identify the asbestos fibers and fiber fragments in the tissue and to characterize the metallome at the cellular level (a pixel size of 2 μm), with a high speed (at 250 Hz). The multielement LA–ICP–TOFMS imaging approach enabled (i) the detection of asbestos fibers/mineral impurities within the MPM tissue samples of patients, (ii) the visualization of the tissue structure with the endogenous elemental pattern at high spatial resolution, and (iii) obtaining insights into the metallome of MPM patients with different pathologies in a single analysis run. Asbestos and other mineral fibers were detected in the lung and pleura tissue of MPM patients, respectively, based on their multielement pattern (Si, Mg, Ca, Fe, and Sr). Interestingly, strontium was detected in asbestos fibers, suggesting a link between this potential toxic element and MPM pathogenesis. Furthermore, monitoring the metallome around the talc deposit regions (characterized by elevated levels of Al, Mg, and Si) revealed significant tissue damage and inflammation caused by talc pleurodesis. LA–ICP–TOFMS results correlated to Perls’ Prussian blue and histological staining of the corresponding serial sections. Ultimately, the ultra-high-speed and high-spatial-resolution capabilities of this novel LA–ICP–TOFMS setup may become an important clinical tool for simultaneous asbestos detection, metallome monitoring, and biomarker identification.
Highlights
Malignant pleural mesothelioma (MPM) is an incurable malignancy associated with high symptom burden and poor prognosis
We have recently demonstrated the potential of high-speed, low-dispersion LA−ICPMS setups to be employed as clinical tools for elemental mapping of asbestos and other mineral fibers within MPM cellular models.[18]
We demonstrate the capabilities of the high-speed, low-dispersion Iridia 193 nm LA system coupled to an icpTOF 2R ICP−TOFMS instrument to spatially resolve different types of asbestos and other mineral fibers within twodimensional (2D) cellular models of MPM and human MPM
Summary
Malignant pleural mesothelioma (MPM) is an incurable malignancy associated with high symptom burden and poor prognosis. Data suggested that crocidolite was characterized by high levels of Na, Mg, Si, and Fe, while amosite and chrysotile yielded elevated Mg, Si, and Fe signals (Figures S3 and S4) These results are in accordance with the nominal composition of the different asbestos fibers[26] and with previous studies using the LA−ICP−sector field MS and LA− ICP−TOFMS instruments.[18,19] it was shown that the LA−ICP−TOFMS method and the selected fluence and laser parameters in this study are fit for the purpose of detecting asbestos fibers within human MPM tissue samples. High-resolution LA−ICP−TOFMS imaging was performed on MPM patient samples of different stages in the pathological presentation and tumor localization including the lung, pleura, and chest wall (Table S2). The glycolytic metabolism is accelerated in cancer cells producing high levels of sulfur-rich compounds via the Maillard reaction.[45]
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