【摘要】 目的:在纳米水平直观验证表皮生长因子受体(EGFR)和肝细胞生长因子受体(c-Met)是否可以结合形成异源二聚体。方法:采用链霉亲和素-生物素技术,利用2种不同大小的纳米金颗粒(10和30 nm)分别结合核酸适配体对EGFR和c-Met进行共标记和共定位;采用环境扫描电镜对2种膜蛋白进行纳米尺度下的超高分辨成像观察,并开展统计分析。结果:三阴性乳腺癌细胞膜表面EGFR单体、二聚体、多聚体的占比分别为48.60%、29.83%、21.57%,cMet单体、二聚体、多聚体的占比分别为38.24%、27.66%、34.10%;EGFR、c-Met可以聚合形成异源二聚体和多聚体,分别占二聚体和多聚体总数的13.71%和24.42%。结论:EGFR和c-Met可以通过形成不同类型聚体的形式在膜上发挥作用,提示联合靶向EGFR和c-Met将成为针对三阴性乳腺癌的一种新的潜在治疗方法。更多还原

【Abstract】 Objective: To visually verify that epidermal growth factor receptor(EGFR) and cellular mesenchymalepithelial transition factor(c-Met) can combine to form heterodimers at the nanometer level. Methods: EGFR and c-Met were co-localized using two streptavidin-labelled gold nanoparticlesof different sizes(10 and 30 nm) respectively combined with biotin-labelled EGFR and c-Met nucleic acid aptamers. Environmental scanning electron microscopy was used to observe the ultra-high resolution imaging of two membrane proteins at the nanoscale, and statistical analysis was performed. Results: The proportions of EGFR monomers, dimers, and multimers on the surface of triple-negative breast cancer(TNBC) cell membranes were 48.60%, 29.83% and 21.57%, respectively; the proportions of c-Met monomers, dimers, and multimers were 38.24%, 27.66% and 34.10%, respectively. EGFR and c-Met can polymerize to form heterodimers and multimers, which account for 13.71% and 24.42% of the total number of dimers and multimers, respectively. Conclusion: EGFR and c-Met can play a role on the membrane by forming different types of aggregates, suggesting that the combined targeting of EGFR and c-Met will become a new potential treatment method for TNBC.更多还原