Cancer cells actively release extracellular vesicles (EVs) as important carriers of cellular information to tumor microenvironments. Although the composition and quantity of the proteins contained in EVs are characterized, it remains unknown how these proteins in EVs are related to those in the original cells at the functional level. With epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells as a model oncoprotein, it is studied how distinct types of EVs, microvesicles and exosomes, represent their original cells at the protein and protein–protein interaction (PPI) level. Using the recently developed single‐molecule immunolabeling and co‐immunoprecipitation schemes, the quantity and PPI strengths of EGFRs derived from EVs and the original lung adenocarcinoma cells are determined. It is found that the microvesicles exhibit higher correlations with the original cells than the exosomes in terms of the EGFR levels and their PPI patterns. In spite of these detailed differences between the microvesicles and exosomes, the EGFR PPI strengths measured for EVs generally show a tight correlation with those determined for the original cells. The results suggest that EGFRs contained in EVs closely reflect the cellular EGFR in terms of their downstream signaling capacity.

中文翻译：

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单分子共免疫沉淀揭示了EGFR在细胞外囊泡中的功能遗传。

癌细胞积极释放细胞外囊泡（EVs），作为细胞信息传递给肿瘤微环境的重要载体。尽管表征了电动汽车中所含蛋白质的组成和数量，但仍不清楚电动汽车中的这些蛋白质在功能水平上如何与原始细胞中的蛋白质相关。以肺腺癌细胞中的表皮生长因子受体（EGFR）作为癌蛋白模型，研究了不同类型的EV，微泡和外泌体如何在蛋白质和蛋白质-蛋白质相互作用（PPI）水平上代表其原始细胞。使用最近开发的单分子免疫标记和共免疫沉淀方案，可以确定源自电动汽车和原始肺腺癌细胞的EGFR的数量和PPI强度。已经发现，就EGFR水平和它们的PPI模式而言，微泡与原始细胞相比于外来体显示出更高的相关性。尽管微泡和外泌体之间存在这些详细的差异，但为电动汽车测得的EGFR PPI强度通常与针对原始细胞测得的EGFR PPI强度紧密相关。结果表明，电动汽车中包含的EGFR就其下游信号传导能力而言，紧密反映了细胞EGFR。