Decreased expression of alpha2,8 sialyltransferase and increased expression of beta1,4 N-acetylgalactosaminyltransferase in gastrointestinal cancers.
Gangliosides such as GD3, GM2, and GD2 are abundantly expressed on the cell surfaces of various malignant cells, suggesting the potential for anti-ganglioside antibody therapy for tumors. Anti-ganglioside GD2 antibody treatment is currently undergoing clinical trials for melanoma and neuroblastoma. We previously reported high in vivo antitumor effects of anti-GM2 ganglioside antibody against lung cancer. To determine whether anti-GM2 antibody may be clinically indicated for gastrointestinal cancers, we evaluated the mRNA expression of alpha2,8 sialyltransferase, a GD3 synthase, and beta1,4 N-acetylgalactosaminyltransferase (beta1,4 GalNAc-T), a GM2/GD2 synthase, in gastrointestinal cancers. We performed modified semi-quantitative RT-PCR, which reduces complexity incidental to radiolabeling on samples taken from small surgically removed clinical specimens. Stomach (19/22) and colorectal (21/30) cancers showed decreased expression of alpha2,8 sialyltransferase as compared with respective normal tissues (P < 0.05). In contrast, increased expression of beta1,4 GalNAc-T was detected in both types of tumors. Clinicopathological analysis revealed significantly higher expression level of alpha2,8 sialyltransferase in the poorly differentiated than in the well-differentiated stomach cancer group (P < 0.05). Furthermore, the expression level of alpha2,8 sialyltransferase was significantly decreased in male as compared with female colorectal cancer patients (P < 0.05). These results suggest that expression level of GM2 ganglioside is elevated in gastrointestinal cancer, and that anti-GM2 antibody may be applicable to its treatment.
Koh
Yasuhiro
Y
Pharmacology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Tsunoda
Takuya
T
Iwahashi
Makoto
M
Yamaue
Hiroki
H
Ishimoto
Kiwao
K
Tanimura
Hiroshi
H
Fukumoto
Hisao
H
Nakamura
Takashi
T
Tatsumi
Yasuaki
Y
Shimizu
Mikiko
M
Saijo
Nagahiro
N
Nishio
Kazuto
K
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology*; D015536:Down-Regulation; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis*; D012737:Sex Factors; D012799:Sialyltransferases / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000201:enzymology*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D005732:Gangliosides; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase