Significance of dipeptidyl peptidases as marker enzyme of oral cancer

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Dipeptidyl peptidases(DPP) are classified into four types, I-IV, according to the substrate specificity. Among them, DPP IV specifically hydrolyzes N-terminal glycylprolyl and is present in microsomal membranes, and DPP II specifically cleaves N-terminal lysylalanyl and is mainly in lysosomes. We have reported that serum DPP IV activity was significantly decreased in oral cancer patients whereas serum DPP II activity was significantly increased, suggesting that they become a possible marker of oral cancer. However, what is the precise mechanism for changing serum enzyme activities and at which stage of carcinogenesis the serum enzyme level begins to be changed, are still unknown.In the present study, the enzyme expression in the precancerous and cancerous tissues and the change of serum enzyme activity level were investigated using hamster buccal pouch carcinogenesis with 9,10-dimethyl-1,2-benzanthracene (DMBA). The serum DPP IV level was decreased gradually from the 8th to 10th week when papillomas were induced by DMBA application. The enzyme level was further decreased as carcinoma in situ or early invasive carcinoma developed (p<0.001), and reached to less than half of the normal level at the time when tumors were diagnosed as squamous cell carcinoma histologically. This enzyme level was increased by tumor excision and decreased again by tumor recurrence toward death. In contrast, serum DPP II activity showed a minor increase in the early stage of carcinogenesis, and increased significantly as squamous cell carcinoma developed (p<0.01). This enzyme activity tended to change reciprocally to DPP IV activity. Immunohistological staining with rabbit anti-rat DPP IV serum did not detect the significant difference between normal and precancerous or cancerous tissues.These findings suggest that serum DPP IV and II activities might be useful as tumor-burden markers ; especially, DPP IV activity, which changed from the early stage of carcinogenesis.