State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China.
Nanoscale. 2019 Aug 8;11(31):14879-14886. doi: 10.1039/c9nr03948a.
Globo H, as one of the most crucial cancer-associated carbohydrates, is exclusively overexpressed in a variety of cancers. However, the accurate localization and detailed morphology of globo H at the molecular level remain unclear. Here, we applied direct stochastic optical reconstruction microscopy (dSTORM) and relied on fluorophore-conjugated aptamers to solve the problem. The results showed that globo H organized as clusters on cell membranes with irregular shapes and different sizes from 100 to 300 nm. Significantly, globo H was found to have a higher expression level and larger clusters on various cancer cells than on non-cancer cells, which hinted that its specific distribution could be utilized for cancer diagnosis. Moreover, dual-color dSTORM imaging revealed the colocalization of globo H and other cancer-associated carbohydrates, and the clustering of globo H could be disrupted by the treatment of corresponding glycosidases, which indicated that these carbohydrates might intertwine in spatial organization and function cooperatively in cancers. Our work clarified the clustered distribution of globo H at the nanometer scale and revealed the potential interactions between cancer-associated carbohydrates, which paves the way for further understanding the relationship between the spatial structures and functions of carbohydrates in cancers.
类脂 H 作为一种最为关键的癌症相关碳水化合物，仅在多种癌症中过表达。然而，类脂 H 在分子水平上的准确定位和详细形态仍不清楚。在这里，我们应用直接随机光学重建显微镜（dSTORM）并依赖荧光标记的适体来解决这个问题。结果表明，类脂 H 在细胞膜上呈不规则形状且大小不一（从 100 纳米到 300 纳米）的团簇形式存在。值得注意的是，与非癌细胞相比，各种癌细胞上的类脂 H 表达水平更高且团簇更大，这表明其特定的分布可用于癌症诊断。此外，双色 dSTORM 成像揭示了类脂 H 与其他癌症相关碳水化合物的共定位，并且相应糖苷酶的处理可以破坏类脂 H 的聚类，这表明这些碳水化合物可能在空间组织中相互交织，并在癌症中协同发挥功能。我们的工作阐明了类脂 H 在纳米尺度上的聚类分布，并揭示了癌症相关碳水化合物之间的潜在相互作用，为进一步理解癌症中碳水化合物的空间结构和功能之间的关系奠定了基础。
