Mitchell Michael J, Castellanos Carlos A, King Michael R
Department of Biomedical Engineering, Cornell University, Ithaca, New York, 14853.
Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139.
J Biomed Mater Res A. 2015 Oct;103(10):3407-18. doi: 10.1002/jbm.a.35445. Epub 2015 Mar 30.
The metastatic spread of tumor cells from the primary site to anatomically distant organs leads to a poor patient prognosis. Increasing evidence has linked adhesive interactions between circulating tumor cells (CTCs) and endothelial cells to metastatic dissemination. Microscale biomimetic flow devices hold promise as a diagnostic tool to isolate CTCs and develop metastatic therapies, utilizing E-selectin (ES) to trigger the initial rolling adhesion of tumor cells under flow. To trigger firm adhesion and capture under flow, such devices also typically require antibodies against biomarkers thought to be expressed on CTCs. This approach is challenged by the fact that CTCs are now known to exhibit heterogeneous expression of conventional biomarkers. Here, we describe surfactant-nanotube complexes to enhance ES-mediated capture and isolation of tumor cells without the use of capture antibodies. While the majority of tumor cells exhibited weaker rolling adhesion on halloysite nanotubes (HNT) coated with ES, HNT functionalization with the sodium dodecanoate (NaL) surfactant induced a switch to firm cellular adhesion under flow. Conversely, surfactant-nanotube complexes significantly reduced the number of primary human leukocytes captured via ES-mediated adhesion under flow. The switch in tumor cell adhesion was exploited to capture and isolate tumor cells in the absence of EpCAM antibodies, commonly utilized as the gold standard for CTC isolation. Additionally, HNT-NaL complexes were shown to capture tumor cells with low to negligible EpCAM expression, that are not efficiently captured using conventional approaches.
肿瘤细胞从原发部位转移扩散至解剖学上距离较远的器官会导致患者预后不良。越来越多的证据表明，循环肿瘤细胞（CTC）与内皮细胞之间的黏附相互作用与转移扩散有关。微尺度仿生流动装置有望成为一种诊断工具，用于分离CTC并开发转移治疗方法，利用E选择素（ES）在流动条件下触发肿瘤细胞的初始滚动黏附。为了在流动条件下触发牢固黏附并捕获细胞，此类装置通常还需要针对被认为在CTC上表达的生物标志物的抗体。然而，由于现在已知CTC会表现出传统生物标志物的异质表达，这种方法面临挑战。在此，我们描述了表面活性剂 - 纳米管复合物，可在不使用捕获抗体的情况下增强ES介导的肿瘤细胞捕获和分离。虽然大多数肿瘤细胞在涂有ES的埃洛石纳米管（HNT）上表现出较弱的滚动黏附，但用十二酸钠（NaL）表面活性剂对HNT进行功能化处理可在流动条件下诱导细胞黏附转变为牢固黏附。相反，表面活性剂 - 纳米管复合物显著减少了在流动条件下通过ES介导的黏附捕获的原代人白细胞数量。利用肿瘤细胞黏附的这种转变，在没有常用作CTC分离金标准的EpCAM抗体的情况下捕获和分离肿瘤细胞。此外，研究表明HNT - NaL复合物能够捕获EpCAM表达低至可忽略不计的肿瘤细胞，而传统方法无法有效捕获此类细胞。
