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Label-Free Vibrational and Quantitative Phase Microscopy Reveals Remarkable Pathogen-Induced Morphomolecular Divergence in Tumor-Derived Cells
ACS Sensors ( IF 8.9 ) Pub Date : 2022-05-18 , DOI: 10.1021/acssensors.2c00232
Zhenhui Liu 1 , Sheetal Parida 2, 3 , Shaoguang Wu 2 , Cynthia L Sears 2 , Dipali Sharma 2, 3 , Ishan Barman 1, 2, 4
Affiliation  

Delineating the molecular and morphological changes that cancer cells undergo in response to extracellular stimuli is crucial for identifying factors that promote tumor progression. Label-free optical imaging offers a potentially promising route for retrieving such single-cell information by generating detailed visualization of the morphology and determining alterations in biomolecular composition. The potential of such nonperturbative morphomolecular microscopy for analyzing microbiota–cancer cell interactions has been surprisingly underappreciated, despite the growing evidence of the critical role of dysbiosis in malignant transformations. Here, using a model system of breast cancer cells, we show that label-free Raman microspectroscopy and quantitative phase microscopy can detect biomolecular and morphological changes in single cells exposed to Bacteroides fragilis toxin (BFT), a toxin secreted by enterotoxigenicB. fragilis. Remarkably, using machine learning to elucidate subtle, but consistent, cellular differences, we found that the morphomolecular differences between BFT-exposed and control breast cancer cells became more accentuated after in vivo passage, corroborating our findings that a short-term BFT exposure imparts a long-term effect on cancer cells and promotes a more invasive phenotype. Complementing more classical labeling techniques, our label-free platform offers a global detection approach with measurements representative of the overall cellular phenotype, paving the way for further investigations into the multifaceted interactions between the cancer cell and the microbiota.

中文翻译:

无标记振动和定量相显微镜揭示了肿瘤来源细胞中显着的病原体诱导的形态分子差异

描述癌细胞响应细胞外刺激而发生的分子和形态学变化对于识别促进肿瘤进展的因素至关重要。无标记光学成像通过生成详细的形态可视化和确定生物分子组成的改变,为检索此类单细胞信息提供了一条潜在的有前途的途径。尽管越来越多的证据表明生态失调在恶性转化中的关键作用,但这种非微扰形态分子显微镜在分析微生物群-癌细胞相互作用方面的潜力却出人意料地被低估了。在这里,使用乳腺癌细胞模型系统,我们表明无标记拉曼显微光谱和定量相显微镜可以检测暴露于脆弱拟杆菌毒素 (BFT),一种由产肠毒素的脆弱拟杆菌分泌的毒素。值得注意的是,使用机器学习来阐明细微但一致的细胞差异,我们发现 BFT 暴露和对照乳腺癌细胞之间的形态分子差异在体内传代后变得更加突出,证实了我们的发现,即短期 BFT暴露赋予对癌细胞的长期影响并促进更具侵袭性的表型。作为更经典的标记技术的补充,我们的无标记平台提供了一种全局检测方法,具有代表整体细胞表型的测量值,为进一步研究癌细胞和微生物群之间的多方面相互作用铺平了道路。
更新日期:2022-05-18
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