Tumor cell surface beta 1-4-linked galactose binds to lectin(s) on microvascular endothelial cells and contributes to organ colonization.
Tumor cell surface beta 1-4-linked galactose binds to lectin(s) on microvascular endothelial cells and contributes to organ colonization.
复制标题
DOI：
10.1083/jcb.111.2.773
复制
发表时间：
1990-08
影响因子：
7.8
通讯作者：
Dennis, J W
中科院分区：
文献类型：
--
作者：
Cornil, I;Kerbel, R S;Dennis, J W
作为组织特异性哺乳动物凝集素的配体的细胞表面碳水化合物结构已经涉及胚胎发生、淋巴细胞归巢和肿瘤细胞转移期间的细胞-细胞相互作用。在这份报告中，我们提供的证据表明，β 1-4连接的半乳糖（Gal）残基的N-连接的寡糖表面上的血液出生的肿瘤细胞作为一个配体结合微血管内皮细胞。D36 W25是MDAY-D2淋巴网状肿瘤细胞系的1类糖基化突变体，由于高尔基体UDP-Gal转运蛋白的缺陷，在细胞聚糖中缺乏唾液酸和Gal。在体外使用UDP-Gal和牛半乳糖基转移酶，β 1-4 Gal恢复到细胞表面，并且70%的半乳糖基化聚糖在体外37 ℃下持续8小时。与模拟处理的D36 W25细胞相比，半乳糖基化的D36 W25细胞在体外与微血管内皮细胞单层的结合增加了80%。半乳糖基化D36 W25细胞与内皮细胞的结合增强可被乳糖胺结合白蛋白抑制。与这些观察结果一致，苦马豆素和castinospermine，两种N-连接的加工抑制剂，导致乳糖胺天线的损失抑制野生型MDAY-D2细胞在体外的内皮细胞的结合。将放射性标记的肿瘤细胞注射到同基因小鼠的循环中，显示D36 W25细胞的半乳糖基化导致2-3个以上的肿瘤细胞保留在肺和肝中。此外，D36 W25细胞的半乳糖基化在肿瘤细胞注射后4周的检查中增加了30倍的可见肝转移的数量。这些结果表明，微血管内皮细胞上的β 1- 4Gal结合凝集素可以有助于血液来源的肿瘤细胞的滞留和继发性肿瘤的形成。随着纯化的糖基转移酶的可用性的增加，在1类突变体的表面上的各种碳水化合物序列的重建提供了研究活细胞上的碳水化合物-凝集素相互作用的受控手段。
Cell surface carbohydrate structures acting as ligands for tissue specific mammalian lectins have been implicated in cell-cell interactions during embryogenesis, lymphocyte homing, and tumor cell metastasis. In this report, we provide evidence that beta 1-4 linked galactose (Gal) residues in N-linked oligosaccharides on the surface of blood born tumor cells serve as a ligand for binding to microvascular endothelial cells. D36W25, a class 1 glycosylation mutant of the MDAY- D2 lymphoreticular tumor cell line, lacks sialic acid and Gal in cellular glycans due to a defect in the Golgi UDP-Gal transporter. Using UDP-Gal and bovine galactosyltransferase in vitro, beta 1-4 Gal was restored to the surface of the cells and 70% of the galactosylated glycans persisted for 8 h in vitro at 37 degrees C. Compared to mock- treated D36W25 cells, galactosylated D36W25 cells showed an 80% increase in binding to microvascular endothelial cell monolayers in vitro. The enhanced binding of galactosylated D36W25 cells to endothelial cell was inhibited by the addition of lactosamine- conjugated albumin to the assay. Consistent with these observations, swainsonine and castinospermine, two inhibitors of N-linked processing that result in loss of lactosamine antennae inhibited the binding of wild-type MDAY-D2 cells to endothelial cells in vitro. Injection of radiolabeled tumor cells into the circulation of syngeneic mice, showed that galactosylation of D36W25 cells resulted in 2-3 more tumor cells retained in the lungs and livers. In addition, galactosylation of D36W25 cells increased by 30-fold the number of visible liver metastases on inspection 4 wk after tumor cell injection. These results suggest that beta 1-4Gal-binding lectins on microvascular endothelial cells can contribute to retention and secondary tumor formation of blood born tumor cells. With the increasing availability of purified glycosyltransferases, reconstruction of a variety of carbohydrate sequences on the surface of class 1 mutants provides a controlled means of studying carbohydrate-lectin interactions on viable cells.