Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow
Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow
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DOI：
10.1152/ajpcell.00423.2002
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发表时间：
2003-04-01
影响因子：
5.5
通讯作者：
Konstantopoulos, K
中科院分区：
文献类型：
--
作者：
Burdick, MM;McCaffery, JM;Konstantopoulos, K
本研究旨在探讨在流动条件下介导LS 174 T结肠腺癌细胞与4 h TNF-α刺激的人脐静脉内皮细胞（HUVECs）粘附的分子成分。在1dyn/cm（2）时，大约57%的细胞滚动，然后牢固地贴壁，而其他细胞则继续在内皮上滚动。初始细胞结合主要由内皮E-选择素介导。通过使用神经氨酸酶、糖脂生物合成抑制剂d，l，苏型-1-苯基-2-十六烷酰氨基-3-吡咯烷-1-丙醇.HCl、胰蛋白酶和流式细胞术，显示LS 174 T细胞表达唾液酸化刘易斯（x）（sLe（x））-和二-sLe（x）-修饰的，但不表达sLe（a）-修饰的E-选择素的糖脂和糖蛋白配体。细胞优先采用唾液酸化糖蛋白糖脂的粘附，如测量的转换滚动到坚定的粘附，抗剥离增加的剪切应力，滚动速度。然而，也存在非唾液酸化的E-选择素反受体。此外，LS 174 T α（2）、α（6）和β（1）整联蛋白支持粘附于HUVEC的次要途径。最后，肿瘤细胞附着特异性地增加E-选择素的HUVEC内吞作用。总而言之，这些数据表明了通过唾液酸化糖缀合物、整合素及其各自的反受体的癌细胞-内皮粘附的复杂性。
This study was undertaken to investigate the molecular constituents mediating LS174T colon adenocarcinoma cell adhesion to 4-h TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs) under flow. At 1 dyn/cm(2), similar to57% of cells rolled and then became firmly adherent, whereas others continuously rolled on endothelium. Initial cell binding was primarily mediated by endothelial E-selectin. By using neuraminidase, glycolipid biosynthesis inhibitor d,l,threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol.HCl, trypsin, and flow cytometry, LS174T cells were shown to express sialyl Lewis(x) (sLe(x))- and di-sLe(x)-decorated, but not sLe(a)-decorated, glycolipid and glycoprotein ligands for E-selectin. The cells preferentially employed sialylated glycoproteins over glycolipids in adhesion as measured by conversion of rolling to firm adhesion, resistance to detachment by increased shear stress, and rolling velocity. However, a nonsialylated E-selectin counterreceptor also exists. Furthermore, LS174T alpha(2), alpha(6), and beta(1) integrins support a minor pathway in adhesion to HUVECs. Finally, tumor cell attachment specifically increases HUVEC endocytosis of E-selectin. Altogether, the data indicate the complexity of carcinoma cell-endothelium adhesion via sialylated glycoconjugates, integrins, and their respective counterreceptors.