Increased expression of UDP-galactose transporter messenger RNA in human colon cancer tissues and its implication in synthesis of Thomsen-Friedenreich antigen and sialyl Lewis A/X determinants.
A series of human nucleotide sugar transporters of the Golgi apparatus was recently cloned, including the transporters for UDP-galactose (UDP-Gal), UDP-N-acetylglucosamine (UDP-GlcNAc) and CMP-sialic acid (CMP-SA). We have examined the mRNA expression of these three transporters in human colon cancer tissues by reverse transcription-PCR analysis and compared it with that in nonmalignant colonic mucosa prepared from the same patients. The amount of mRNA for UDP-Gal transporter was significantly increased in colon cancer tissues compared with nonmalignant mucosa tissues (P = 0.035; n = 20). The increase was more prominent in patients with advanced colorectal cancer of Dukes' stages C and D, in which the amount of UDP-Gal transporter mRNA in cancer tissues showed on average about a 3.6-fold increase over the paired nonmalignant mucosa (statistically significant at P = 0.004; n = 14). The mRNA content of the other two transporters showed no significant difference between the paired cancer and normal tissues. When UDP-Gal transporter cDNA was stably transfected to cultured human colon cancer cells, the expression of Thomsen-Friedenreich (TF) antigen and of sialyl Lewis A (NeuAcalpha2-->3Galbeta1-->3[Fucalpha1-->4]GlcNAcbeta1-->R) and sialyl Lewis X (NeuAcalpha2-->3Galbeta1-->4[Fucalpha1-->3]GlcNAcbeta1-->R) determinants was significantly induced on transfectant cells, which resulted in markedly enhanced cell adhesion to vascular E-selectin. These findings suggest that the increase of UDP-Gal transporter mRNA is involved in the enhanced expression of cancer-associated carbohydrate determinants such as TF and sialyl Lewis A/X antigens in colon cancers.
Kumamoto
K
K
Department of Molecular Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusaku, Nagoya 464-8681, Japan.
Goto
Y
Y
Sekikawa
K
K
Takenoshita
S
S
Ishida
N
N
Kawakita
M
M
Kannagi
R
R
D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis*; D018395:CA-19-9 Antigen; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003470:Culture Media; D018076:DNA, Complementary / Q000235:genetics; D005690:Galactose / Q000378:metabolism; D005732:Gangliosides / Q000096:biosynthesis*; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D009844:Oligosaccharides / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000080506:Sialyl Lewis X Antigen; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099237:UDP-Galactose Translocators
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D018395:CA-19-9 Antigen; D003470:Culture Media; D018076:DNA, Complementary; D005690:Galactose; D005732:Gangliosides; D009004:Monosaccharide Transport Proteins; D009844:Oligosaccharides; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; D000099237:UDP-Galactose Translocators; C016467:Thomsen-Friedenreich antigen; C064564:sialyl Le(a) ganglioside