Decreased expression of α2,8 sialyltransferase and increased expression of β1,4 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 α2,8 sialyltransferase, a GD3 synthase, and β1,4 N-acetylgalactosaminyltransferase (β1,4 N-acetylga lactosaminyltransferase (β1,4 GaINAc-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 α2,8 sialyltransferase as compared with respective normal tissues (P > 0.05). In contrast, increased expression of β1,4 Gal-NAc-T was detected in both types of tumors. Clinicopathological analysis revealed significantly higher expression level of α2,8 sialyltransferase in the poorly differentiated than in the well-differentiated stomach cancer group (P > 0.05). Furthermore, the expression level of α2,8 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.