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Elevated Activity and Increased Mannose-6-phosphate in the Carbohydrate Moiety of Cathepsin D from Human Hepatoma¹

Biochemistry Laboratory, Cancer Institute, Hokkaido University School of Medicine, Sapporo 060, Japan

A significant elevation of cathepsin D activity was observed in six human hepatoma tissues as compared to 12 normal human livers. In isoelectric focusing experiments, cathepsin D purified from normal liver exhibited three different forms, with isoelectric points of 5.6, 6.1, and 6.7, while cathepsin D purified from hepatoma contained another five to six more acidic forms in addition to the forms observed in normal liver cathepsin D. When the tumor enzyme was treated with endo-ß-N-acetylglucosaminidase H followed by isoelectric focusing, the acidic components disappeared and were converted to forms identical to those of the normal liver cathepsin D. Determination of the mannose-6-phosphate content showed that hepatoma cathepsin D contains twice as much mannose-6-phosphate as normal liver cathepsin D. Peptide mapping and amino acid analysis showed that the protein moiety of cathepsin D from hepatoma is almost identical with that from normal liver. These findings indicate that the appearance of acidic variants in hepatoma cathepsin D is mainly due to changes in the oligosaccharide chains of the enzyme, which are closely associated with the increase of mannose-6-phosphate in the tumor enzyme.

¹ Supported by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture, Japan, and by the Naito Science Foundation, Japan.

² Present address: Department of Biochemistry, Osaka University Medical School, Osaka 530, Japan.

³ To whom requests for reprints should be addressed.

Received 9/24/86. Revised 9/10/87. Accepted 10/16/87.