One critical step of metastasis formation is the extravasation of circulating tumor cells from the bloodstream. This process requires the dynamic interaction of cell adhesion molecules like E-selectin on endothelial cells with carbohydrate ligands on tumor cells. To characterize these glycans in a comprehensible approach, the rolling, tethering, and firm adhesion of nine human tumor cell lines on human umbilical vein endothelial cells was analyzed using laminar flow adhesion assays. The tumor cell lines were grouped into three subsets by their canonical E-selectin ligand status (sialyl-Lewis A and X +/+, -/+, -/-) and their adhesiveness was compared after enzymatic, pharmacologic, chemical treatment or antibody blockade of the tumor cells or endothelial cells, respectively. Tumor cells were also screened regarding their glycosyltransferase expression profile. We found that although E-selectin and terminal α2,3-sialic acid largely determined firm adhesion, adhesive events did not exclusively depend on the presence of sialyl-Lewis A and/or sialyl-Lewis X. Nevertheless, two of the three sialyl-Lewis A/X-/- tumor cells additionally or fully depended on vascular cell adhesion molecule-1 for firm adhesion. The significance of O-GalNAc- and N-glycans for adhesion varied remarkably among the tumor cells. The sialyl-Lewis A/X+/+ subset showed glycoprotein-independent adhesion, suggesting a role of glycolipids as well. All sialyl-Lewis A/X-/- tumor cells lacked FUT3 and FUT7 expression as opposed to sialyl-Lewis A/X+/+ or -/+ cell lines. In summary, the glycans on tumor cells mediating endothelial adhesion are not as much restricted to sialyl-Lewis A /X as previously assumed. The present study specifically suggests α2,3-linked sialic acid, O-GalNAc glycans, glycosphingolipids, and FUT3/FUT7 products as promising targets for future studies.

中文翻译：

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鉴定介导人类肿瘤细胞动态内皮粘附的潜在糖配体类别。

转移形成的关键步骤之一是循环肿瘤细胞从血流中外渗。这个过程需要细胞粘附分子（如内皮细胞上的 E-选择素）与肿瘤细胞上的碳水化合物配体的动态相互作用。为了以可理解的方法表征这些聚糖，使用层流粘附测定分析了九种人类肿瘤细胞系在人脐静脉内皮细胞上的滚动、束缚和牢固粘附。根据其典型的 E-选择素配体状态（唾液酸-Lewis A 和 X +/+、-/+、-/-）将肿瘤细胞系分为三个子集，并在酶促、药物、化学处理或抗体处理后比较它们的粘附性分别阻断肿瘤细胞或内皮细胞。还对肿瘤细胞的糖基转移酶表达谱进行了筛选。我们发现，虽然 E-选择素和末端 α2,3-唾液酸在很大程度上决定了牢固的粘附，但粘附事件并不完全取决于唾液酸-刘易斯 A 和/或唾液酸-刘易斯 X 的存在。尽管如此，三个唾液酸中的两个 - Lewis A/X-/-肿瘤细胞另外或完全依赖于血管细胞粘附分子-1来实现牢固粘附。O-GalNAc-和N-聚糖对于粘附的重要性在肿瘤细胞之间存在显着差异。唾液酸-刘易斯 A/X+/+ 子集显示出不依赖于糖蛋白的粘附，表明糖脂也发挥了作用。与唾液酸-Lewis A/X+/+ 或 -/+ 细胞系相反，所有唾液酸-Lewis A/X-/- 肿瘤细胞均缺乏 FUT3 和 FUT7 表达。总之，肿瘤细胞上介导内皮粘附的聚糖并不像之前假设的那样仅限于唾液酸-Lewis A /X。本研究特别建议 ​​α2,3 连接唾液酸、O-GalNAc 聚糖、鞘糖脂和 FUT3/FUT7 产品作为未来研究的有希望的目标。