CARCINOMA-ASSOCIATED EXPRESSION OF CORE-2 BETA-1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE GENE IN HUMAN COLORECTAL-CANCER - ROLE OF O-GLYCANS IN TUMOR PROGRESSION

Recently, it was demonstrated that an increased level of NeuNAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta-R (sialyl Le(x)) and NeuNAc alpha 2-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc beta-R (sialyl Lea) express ion on the surface of colorectal cancer cells is positively correlated with progression of the disease. It has not been determined, however, which type of glycans, N- or O-glycans, is more closely associated wi th progression when cancer cells express those oligosaccharides. To ad dress this problem, we have examined expression of sialyl Le(a) and si alyl Le(x), those oligosaccharides in O-glycans, and core 2 beta-1,6-N -acetylglucosaminyltransferase (C2GnT) transcripts in colorectal cance r specimens from 46 patients and compared those results with clinicopa thological variables, C2GnT is a glycosyltransferase that is responsib le for the core 2 branch, which is critical for biosynthesis of sialyl Le(a) and sialyl Le(x) in O-glycans. Sialyl Le(a) and sialyl Le(x) we re determined by immunohistochemistry, and C2GnT transcripts were dete cted by reverse transcription-PCR. Sialyl Le(a) or sialyl Le(x) in O-g lycans was assessed by combining immunohistochemistry for sialyl Le(a) or sialyl Le(x) with reverse transcription-PCR for C2GnT, Sialyl Le(a ), detected on cancer cells in 74% of patients, was well correlated wi th lymph node metastasis, whereas sialyl Le(a) and sialyl Le(x) in O-g lycans, which were specifically detected in cancer tissues of 50 and 6 1% of patients, respectively, were closely associated with lymphatic a nd venous invasion, In addition, C2GnT, which was specifically detecte d in cancer tissues of 63% of patients, was closely correlated with th e vessel invasion, as well as depth of tumor invasion, These results s trongly suggest that sialyl Le(a) and sialyl Le(x) in O-glycans and C2 GnT, expressed in cancer cells, may play important roles in tumor prog ression through vessel or direct invasion.