岩藻糖链与肝癌细胞发生和转移的相关性研究(英文)

Fucosylated Glycans Associated With Development and Metastasis of Hepatocellular Carcinoma Cells

研究观察了大鼠诱发肝癌过程中,与UEA、LCA凝集素相结合的含岩藻糖糖蛋白尤其是80ku蛋白的动态变化.在肝癌病人标本中,也观察到了高转移性肝癌细胞比低转移性肝癌细胞表达更多的UEA、LCA相结合的岩藻糖蛋白.岩藻糖寡糖可以构成一些非常重要的黏附分子的结构,如Lewis抗原.继而进一步观察了不同转移潜能的肝癌细胞中Lewis抗原的表达差异,发现高转移性肝癌细胞(HMCC97H)比低转移性肝癌细胞(HMCC97L)表达更高的Lewisx和b.在肝癌转移动物模型中,转移灶组织中的Lewis抗原合成关键酶α1,3/1,2以及α1,6岩藻糖转移酶活性远比对照组高.当肝癌细胞在维甲酸作用以后,细胞表面的Lewisx或b的水平显著下降,α1,3/1,2岩藻糖转移酶活性也显著下降.同时我们观察到Lewisx可以存在于表皮细胞生长因子受体(EGFR)分子上,在维甲酸作用以后,EGFR上的Lewisx抗原和磷酸化水平都显著性下降.上述结果提示岩藻糖化的糖链如Lewisx在肝癌细胞的发生和转移过程中起重要的作用.

Dynamic fucosylation of glycoprotein especially 80 ku which bound to UEA and LCA during the course of rat hepatocarcinogenesis was investigated. In patient hepatocellular carcinoma, more UEA- and LCA-bound proteins were also observed in patients with high metastatic potential than those with low metastatic potential. Fucosylated glycans constitute important adhesion molecules such as Lewis antigens. A differential expression pattern of Lewis antigens was further confirmed on various metastasis potential hepatocellular carcinoma cells （HCC）. High metastatic hepatocellular carcinoma cell line （HMCC97H） expressed much more Lewis x and b than low metastasis HMCC97L cells. Moreover, surface Lewis x, or b expression level declined significantly after the cells were treated by retinoic acid. Not only in experimental metastasis loci, but in HCC as well, bothα1,3/1,2 and α1,6 fucosyltransferase activities were quite high. After retinoic acid treatment, α1,3/1,2 fucosyltransferase activities were significantly inhibited, Lewis x on epidermal growth factor receptor reduced, and the EGFR was less phosphorylated. These results suggested that fucosylated glycans such as Lewis x played an important role in HCC development and metastasis.