Department of Biomedical Engineering, Cornell University Ithaca, NY, USA.
Front Oncol. 2012 Jul 27;2:76. doi: 10.3389/fonc.2012.00076. eCollection 2012.
glycoprotein interactions which lead to eventual extravasation and metastases. The aberrantly underglycosylated mucin MUC1 has been shown to both abundantly express selectin binding moieties (sialyl Lewis x and a) and to consistently expose its core epitope. Flow cytometry was used to determine MUC1 expression on ZR-75-1 and MCF7 cells, while immunofluorescence microscopy was used to confirm the aberrant form of MUC1 and MUC1:ICAM-1 interactions. Each cell line was then perfused through combined E-selectin and ICAM-1 coated microtubes, as a model of the microvascular endothelium. ZR-75-1 and MCF7 were found to express abundant and low levels of underglycosylated MUC1, respectively. The rolling/adhesion profiles showed that ZR-75-1 cells, when compared to MCF7 cells, interact with E-selectin more efficiently resulting in sufficiently slow rolling velocities to form MUC1:ICAM-1 interactions thereby facilitating firm adhesion. The purpose and novelty of this work is the demonstration of the synergistic adhesion capabilities of MUC1 in the metastatic adhesion cascade, where the observed differential adhesion is consistent with the relative metastatic potential of the ZR-75-1 (highly metastatic) and MCF7 (weakly metastatic) cell lines.
肿瘤细胞在血管壁上的黏附和滚动是由各种选择素与糖蛋白的相互作用所促进的，这些作用最终导致了肿瘤细胞的渗出和转移。异常低聚糖化的黏蛋白 MUC1 已被证明大量表达选择素结合部位（唾液酸化 Lewis x 和 a），并持续暴露其核心表位。我们利用流式细胞术来确定 ZR-75-1 和 MCF7 细胞上 MUC1 的表达情况，同时利用免疫荧光显微镜来确认异常形式的 MUC1 和 MUC1:ICAM-1 相互作用。然后，我们将每种细胞系通过包被 E-选择素和 ICAM-1 的微管进行灌注，作为微血管内皮的模型。结果发现，ZR-75-1 和 MCF7 分别表达丰富和低水平的异常低聚糖化 MUC1。滚动/黏附谱显示，与 MCF7 细胞相比，ZR-75-1 细胞与 E-选择素的相互作用更有效，导致足够缓慢的滚动速度，从而形成 MUC1:ICAM-1 相互作用，从而促进牢固的黏附。这项工作的目的和新颖之处在于展示了 MUC1 在转移性黏附级联反应中的协同黏附能力，观察到的差异黏附与 ZR-75-1（高转移性）和 MCF7（低转移性）细胞系的相对转移性潜力一致。
