Quantitative analysis of ß1,6GlcNAc-branched N-glycans on ß4 integrin in cutaneous squamous cell carcinoma.

α6ß4 integrin plays pivotal roles in cancer progression in several types of cancers. Our previous study using N-glycan-manipulated cell lines demonstrated that defects in N-glycans or decreased ß1,6GlcNAc-branched N-glycans on ß4 integrin suppress ß4 integrin-mediated cancer cell adhesion, migration, invasion, and tumorigenesis. Furthermore, immunohistochemical analysis has shown that colocalization of ß1,6GlcNAc-branched N-glycans with ß4 integrin was observed in cutaneous squamous cell carcinoma (SCC) tissue. However, until now there has been no direct evidence that ß1,6GlcNAc-branched N-glycans are upregulated on ß4 integrin in cutaneous SCC. In the present study, we performed an ELISA analysis of ß1,6GlcNAc-branched N-glycans on ß4 integrins as well as ß4 integrins in cell lysates from human normal skin and cutaneous SCC tissues. The SCC samples showed a 4.9- to 7.4-fold increase in the ratio of ß1,6GlcNAc-branched N-glycans to ß4 integrin compared with normal skin samples. These findings suggest that the addition of ß1,6GlcNAc-branched N-glycans onto ß4 integrin was markedly elevated in cutaneous SCC tissue compared to normal skin tissue. The value of ß1,6GlcNAc-branched N-glycans on ß4 integrin may be useful as a diagnostic marker associated with cutaneous SCC tumor progression.