Demonstration of proteases in basal cell carcinomas. A histochemical study using amino acid-4-methoxy-2-naphthylamides as chromogenic substrates.

BACKGROUND

Proteases are reported to play an essential part in the proliferative, invasive, and metastasizing behavior of malignant tumors. The aim of the current study was to determine the activity and localization of proteases in basal cell carcinomas (BCC) histochemically.

METHODS

Various proteases were identified histochemically in frozen sections of BCC. The following amino acid-4-methoxy-2-naphthylamides (MNA) were used as chromogenic substrates:alanine-MNA for the detection of aminopeptidase M (APM), glycyl-proline-MNA for dipeptidyl peptidase IV (DPP IV), lysyl-proline-MNA and lysyl-alanine-MNA for dipeptidyl peptidase II (DPP II), glycyl-arginine-MNA for dipeptidyl peptidase I (DPP I), and carbobenzoxy (CBZ)-arginyl-arginine-MNA for cathepsin B.

RESULTS

APM activity was high in the peritumorous connective tissue, whereas the tumor epithelium and epidermis had negative results. DPP IV showed a highly positive reaction in both tumor epithelium and surrounding connective tissue. Cathepsin B and DPP I reacted strongly in the tumor epithelium but not in the peritumorous connective tissue.

CONCLUSIONS

The marked activity of APM, DPP IV, DPP I, and cathepsin B may be related to the proliferation and invasive growth of BCC. The distribution of the activity of APM and DPP IV indicates dynamic interactions between the tumor epithelium and the adjacent connective tissue in the neoplastic process.