2015年7月22日訊 /生物谷BIOON/ --近日，來自德國的科學家發現HER2二聚體在一小群休眠的SKBR3乳腺癌細胞中發生缺失，這一群細胞具有自我更新的特性，可能在靶向HER2的抗體治療過程中促進了乳腺癌細胞對此類抗體藥物的抵抗，導致新的腫瘤形成。
HER2是屬於EGFR受體家族的一類膜蛋白，通常情況下當該家族成員受到外界信號刺激，可以形成二聚體，觸發細胞生長信號，但HER2比較特別，其可以在沒有外界信號刺激的情況下發生二聚化調節細胞生長。在之前一些研究中發現HER2在一些特定類型的乳腺癌中發揮重要作用：HER2表達水平增加會導致細胞發生無限生長。目前有一些靶向HER2的抗體療法可以發揮阻止癌細胞生長的作用，但有大約三分之二的HER2陽性乳腺癌病人會對HER2靶向性藥物產生抵抗，其中的原因一直不明。
在這項研究中，研究人員利用螢光顯微鏡和環境掃描電子顯微鏡技術在納米水平上對液體環境下的完整細胞結構進行了研究。他們將細胞接種在微晶片上，使細胞處於液體環境中，隨後將微晶片放在電子顯微鏡下進行觀察，這種方法克服了傳統電鏡方法無法對液體環境下完整細胞進行觀察的技術障礙。
利用這種新技術研究人員對HER2膜蛋白的局部改變及其二聚體的形成進行了觀察，結果發現在一小群休眠的SKBR3細胞中，HER2二聚體會發生缺失。但這一小群細胞是否在靶向治療過程中存活下來並在乳腺癌後期導致藥物抵抗的發生還需要更多的研究進行證明。
生物谷小編認為這項研究利用一種新的電子顯微鏡技術對乳腺癌細胞膜上的HER2進行了觀察，在一小群休眠的SKBR3乳腺癌細胞中發現存在HER2二聚體缺失，並提出這可能是導致乳腺癌病人抵抗HER2抗體靶向療法的重要原因。
相關研究結果發表在國際學術期刊science advances上。（生物谷Bioon.com）
Local variations of HER2 dimerization in breast cancer cells discovered by correlative fluorescence and liquid electron microscopy
Diana B. Peckys1, Ulrike Korf2 and Niels de Jonge
The formation of HER2 homodimers plays an important role in breast cancer aggressiveness and progression; however, little is known about its localization. We have studied the intra- and intercellular variation of HER2 at the single-molecule level in intact SKBR3 breast cancer cells. Whole cells were visualized in hydrated state with correlative fluorescence microscopy and environmental scanning electron microscopy (ESEM). The locations of individual HER2 receptors were detected using an anti-HER2 affibody in combination with a quantum dot (QD), a fluorescent nanoparticle. Fluorescence microscopy revealed considerable differences of HER2 membrane expression between individual cells and between different membrane regions of the same cell (that is, membrane ruffles and flat areas). Subsequent ESEM of the corresponding cellular regions provided images of individually labeled HER2 receptors. The high spatial resolution of 3 nm and the close proximity between the QD and the receptor allowed quantifying the stoichiometry of HER2 complexes, distinguishing between monomers, dimers, and higher-order clusters. Downstream data analysis based on calculating the pair correlation function from receptor positions showed that cellular regions exhibiting membrane ruffles contained a substantial fraction of HER2 in homodimeric state. Larger-order clusters were also present. Membrane areas with homogeneous membrane topography, on the contrary, displayed HER2 in random distribution. Second, HER2 homodimers appeared to be absent from a small subpopulation of cells exhibiting a flat membrane topography, possibly resting cells. Local differences in homodimer presence may point toward functional differences with possible relevance for studying metastasis and drug response.