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Experimental Biology and Medicine 227:196-200 (2002)
© 2002 Society for Experimental Biology and Medicine

ORIGINAL ARTICLE

Decreased Expression of {alpha}2,8 Sialyltransferase and Increased Expression of ß1,4 N-Acetylgalactosaminyltransferase in Gastrointestinal Cancers

Yasuhiro Koh*, Takuya Tsunoda{ddagger}, Makoto Iwahashi{dagger}, Hiroki Yamaue{dagger}, Kiwao Ishimoto{dagger}, Hiroshi Tanimura{dagger}, Hisao Fukumoto*, Takashi Nakamura*, Yasuaki Tatsumi*, Mikiko Shimizu*, Nagahiro Saijo* and Kazuto Nishio*,1

* Pharmacology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan;
{dagger} 2nd Department of Surgery, Wakayama Medical School, Wakayama 641-0012, Japan; and
{ddagger} Department of Surgery and Bioengineering Advanced Clinical Research Center, Institute of Medical Science of Tokyo, 108-8639, Japan

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 {alpha}2,8 sialyltransferase, a GD3 synthase, and ß1,4 N-acetylgalactosaminyltransferase (ß1,4 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 {alpha}2,8 sialyltransferase as compared with respective normal tissues (P < 0.05). In contrast, increased expression of ß1,4 GalNAc-T was detected in both types of tumors. Clinicopathological analysis revealed significantly higher expression level of {alpha}2,8 sialyltransferase in the poorly differentiated than in the well-differentiated stomach cancer group (P < 0.05). Furthermore, the expression level of {alpha}2,8 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.

Key Words: gastrointestinal cancer • ganglioside • ß1,4 N-acetylgalactosaminyltransferase • {alpha}2,8 sialyltransferase






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Copyright © 2002 by the Society for Experimental Biology and Medicine.