Human plasma membrane-associated sialidase (Neu3) is unique in specifically hydrolyzing gangliosides, thought to participate in cell differentiation and transmembrane signaling, thereby playing crucial roles in the regulation of cell surface functions. We have discovered levels of mRNA for this sialidase to be increased in restricted cases of human colon cancer by 3-to 100-fold compared with adjacent nontumor mucosa (n ‫؍‬ 32), associated with significant elevation in sialidase activity in tumors (n ‫؍‬ 50). In situ hybridization showed the sialidase expression in epithelial elements of adenocarcinomas. In cultured human colon cancer cells, the sialidase level was downregulated in the process of differentiation and apoptosis induced by sodium butyrate, whereas lysosomal sialidase (Neu1) was upregulated. Transfection of the sialidase gene into colon cancer cells inhibited apoptosis and was accompanied by increased Bcl-2 and decreased caspase expression. Colon cancer exhibited a marked accumulation of lactosylceramide, a possible sialidase product, and addition of the glycolipid to the culture reduced apoptotic cells during sodium butyrate treatment. These results indicate that high expression of the sialidase in cancer cells leads to protection against programmed cell death, probably modulation of gangliosides. This finding provides a possible sialidase target for diagnosis and therapy of colon cancer.

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BACKGROUND.In colorectal carcinoma, venous invasion has been related to patient

LC is not likely to worsen the survival rate of patients with GBC compared with the survival rate of patients undergoing a standard open radical procedure, as long as additional excision is conducted for patients with laparoscopically removed pT2 or pT3 GBCs. Special attention should be paid to prevention of bile spillage during LC.