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 alpha2-3Gal beta1-4(Fuc alpha1-3)GlcNAc beta-R (sialyl Le(x)) and NeuNAc alpha2-3Gal beta1-3(Fuc alpha1-4)GlcNAc beta-R (sialyl Le(a)) expression 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 with progression when cancer cells express those oligosaccharides. To address this problem, we have examined expression of sialyl Le(a) and sialyl Le(x), those oligosaccharides in O-glycans, and core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) transcripts in colorectal cancer specimens from 46 patients and compared those results with clinicopathological variables. C2GnT is a glycosyltransferase that is responsible 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) were determined by immunohistochemistry, and C2GnT transcripts were detected by reverse transcription-PCR. Sialyl Le(a) or sialyl Le(x) in O-glycans 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 with lymph node metastasis, whereas sialyl Le(a) and sialyl Le(x) in O-glycans, which were specifically detected in cancer tissues of 50 and 61% of patients, respectively, were closely associated with lymphatic and venous invasion. In addition, C2GnT, which was specifically detected in cancer tissues of 63% of patients, was closely correlated with the vessel invasion, as well as depth of tumor invasion. These results strongly suggest that sialyl Le(a) and sialyl Le(x) in O-glycans and C2GnT, expressed in cancer cells, may play important roles in tumor progression through vessel or direct invasion.
Shimodaira
K
K
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Nakayama
J
J
Nakamura
N
N
Hasebe
O
O
Katsuyama
T
T
Fukuda
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D018395:CA-19-9 Antigen; D002240:Carbohydrate Sequence; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005732:Gangliosides / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis / Q000737:chemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009844:Oligosaccharides / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D016133:Polymerase Chain Reaction; D000080506:Sialyl Lewis X Antigen; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D005732:Gangliosides; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; C064564:sialyl Le(a) ganglioside; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase