Bironaite D, Nesland J M, Dalen H, Risberg B, Bryne M
Institute of Biochemistry, Lithuanian Academy of Sciences, Vilnius, Lithuania.
Tumour Biol. 2000 May-Jun;21(3):165-75. doi: 10.1159/000030123.
Alterations in cellular glycosylation may play a key role in metastatic behaviour of tumour cells. We studied three metastatic cell lines, LOX (malignant melanoma), FEMX (malignant melanoma) and MA-11 (mammary carcinoma). These cell lines have a very different metastatic behaviour in vivo, and different glycans have been postulated to be partly responsible for these differences. To further investigate the functional role of carbohydrates, these three cell lines have been treated with tunicamycin, an inhibitor of the biosynthesis of N-glycans and benzyl- alpha-N-acetylgalactosamine (benzyl-alpha-GalNAc; BnGalNAc), an inhibitor of mature O-linked glycans. Various in vitro adhesion and invasion assays were undertaken for functional studies. Tunicamycin significantly inhibited adhesion to laminin, but only slightly affected cell adhesion to collagen IV. The same compound significantly decreased cellular invasiveness through a Matrigel invasion chamber. Moreover, tunicamycin reduced homotypic aggregation of cells. BnGalNAc had generally little effect on cell behaviour in in vitro assay. The effects of the inhibitors were, however, to some extent cell line-specific. We conclude that N-glycans, but probably not mature O-glycans have important in vitro functions in cell adhesion to laminin, cell invasion through Matrigel and cellular aggregation in the studied cell lines. These results support the view that carbohydrates are functionally involved in several steps of the metastatic process.
细胞糖基化的改变可能在肿瘤细胞的转移行为中起关键作用。我们研究了三种转移细胞系，即LOX（恶性黑色素瘤）、FEMX（恶性黑色素瘤）和MA - 11（乳腺癌）。这些细胞系在体内具有非常不同的转移行为，并且推测不同的聚糖部分地导致了这些差异。为了进一步研究碳水化合物的功能作用，用衣霉素（一种N - 聚糖生物合成抑制剂）和苄基 - α - N - 乙酰半乳糖胺（苄基 - α - GalNAc；BnGalNAc，一种成熟O - 连接聚糖抑制剂）处理这三种细胞系。进行了各种体外黏附与侵袭试验以进行功能研究。衣霉素显著抑制对层粘连蛋白的黏附，但仅轻微影响细胞对IV型胶原的黏附。同一化合物显著降低细胞通过基质胶侵袭小室的侵袭能力。此外，衣霉素减少细胞的同型聚集。BnGalNAc在体外试验中对细胞行为通常影响很小。然而，抑制剂的作用在一定程度上具有细胞系特异性。我们得出结论，在所研究的细胞系中，N - 聚糖而非成熟的O - 聚糖在细胞对层粘连蛋白的黏附、通过基质胶的细胞侵袭及细胞聚集中具有重要的体外功能。这些结果支持碳水化合物在转移过程的多个步骤中具有功能作用这一观点。
