Dennis J W, Laferté S, Yagel S, Breitman M L
Division of Cancer and Cell Biology, Mount Sinai Hospital Research Institute, Ontario, Canada.
Cancer Cells. 1989 Nov;1(3):87-92.
Malignant transformation and tumor progression are often accompanied by structural changes in the carbohydrate components of glycoproteins and glycolipids. Studies with tumor cell glycosylation mutants and specific inhibitors of glycosylation indicate that expression of sialylated and beta (1-6) branched asparagine (Asn)-linked oligosaccharides are required for tumor cell invasion and metastasis. The initiation of the beta (1-6) antenna appears to be oncodevelopmentally regulated and may be associated with the aberrant expression of blood group and embryonic carbohydrate sequences in Asn-linked oligosaccharides of tumors. Although the function of these oligosaccharides in the metastatic process remains unclear, there is some evidence that expression of these structures on certain cell-surface glycoproteins may reduce tumor cell adhesion to extracellular matrix. These observations suggest that low-toxicity drugs that inhibit the biosynthesis of these structures may be useful in the treatment of metastatic cancers.
恶性转化和肿瘤进展通常伴随着糖蛋白和糖脂碳水化合物成分的结构变化。对肿瘤细胞糖基化突变体和糖基化特异性抑制剂的研究表明,唾液酸化和β(1-6)分支天冬酰胺(Asn)连接的寡糖的表达是肿瘤细胞侵袭和转移所必需的。β(1-6)天线的起始似乎受到肿瘤发生发展调控,并且可能与肿瘤Asn连接寡糖中血型和胚胎碳水化合物序列的异常表达有关。尽管这些寡糖在转移过程中的功能尚不清楚,但有证据表明这些结构在某些细胞表面糖蛋白上的表达可能会降低肿瘤细胞与细胞外基质的粘附。这些观察结果表明,抑制这些结构生物合成的低毒性药物可能对转移性癌症的治疗有用。