Izumi Y, Taniuchi Y, Tsuji T, Smith C W, Nakamori S, Fidler I J, Irimura T
Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Exp Cell Res. 1995 Jan;216(1):215-21. doi: 10.1006/excr.1995.1027.
The content of sialyl Lewis-X antigen (Neu5Ac alpha 2-3Gal beta 1-4(fuc alpha 1-3)GlcNAc-R: sialyl Le(x)) was previously shown to correlate with the progression of human colon carcinomas to the advanced stages. Variant cell lines with high (KM12-HX) or low (KM12-LX) levels of cell surface sialyl Le(x) were isolated from the heterogeneous KM12C cells to characterize the biological behavior of colon carcinoma cells with elevated cell surface contents of sialyl Le(x). When these cells were injected intrasplenically into nude mice, KM12-HX cells colonized to the liver more efficiently than KM12-LX cells. Under in vitro conditions, KM12-HX cells demonstrated greater degree of adhesion to cytokine-activated human umbilical vein endothelial cells than KM12-LX cells. The adhesion of KM12-HX cells was partially inhibited by antibodies specific for E-selectin, which was known to serve as a ligand for the sialyl Le(x) carbohydrate antigen. The treatment of KM12-HX cells with benzyl N-acetyl-alpha-D-galactosaminide, a putative inhibitor of the extension of O-linked carbohydrate chains, reduced the rate of adhesion. These results suggested that the interaction of endothelial cell surface E-selectin with O-linked carbohydrate chains on colon carcinoma cell surface glycoproteins played an important role in the adhesion.
唾液酸化路易斯-X抗原（Neu5Acα2-3Galβ1-4（fucα1-3）GlcNAc-R：唾液酸化Le(x)）的含量先前已被证明与人类结肠癌进展至晚期相关。从异质性的KM12C细胞中分离出具有高（KM12-HX）或低（KM12-LX）细胞表面唾液酸化Le(x)水平的变异细胞系，以表征细胞表面唾液酸化Le(x)含量升高的结肠癌细胞的生物学行为。当将这些细胞经脾内注射到裸鼠体内时，KM12-HX细胞比KM12-LX细胞更有效地在肝脏中定植。在体外条件下，KM12-HX细胞比KM12-LX细胞对细胞因子激活的人脐静脉内皮细胞表现出更高程度的黏附。KM12-HX细胞的黏附被对E-选择素特异的抗体部分抑制，已知E-选择素作为唾液酸化Le(x)碳水化合物抗原的配体。用苄基N-乙酰-α-D-半乳糖胺（一种推测的O-连接碳水化合物链延伸抑制剂）处理KM12-HX细胞，降低了黏附率。这些结果表明内皮细胞表面E-选择素与结肠癌细胞表面糖蛋白上的O-连接碳水化合物链之间的相互作用在黏附中起重要作用。
