岩藻糖链与肝癌细胞发生和转移的相关性研究

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80 ku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Lewis x 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Lewis x 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Lewis x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Lewis x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Lewis x在肝癌细胞的发生和转移过程中起重要的作用．

Fucosylated Glycans Associated With Development and Metastasis of Hepatocellular Carcinoma Cells

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. Fueosylated glycans constitute important adhesion molecules such as Lewis antigens. A differential expression pattern of Lewis antigens was further conf'Lrmed 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 retinoie acid. Not only in experimental metastasis foei, but in HCC as well, both α1,3/1,2 and α1,6 fucosyltransferase activities were quite high. After retinoie acid treatment, α1,3/1,2 fueosyltransferase 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.