Activity, expression, and transcription rate of the cathepsins B, D, H, and L in cutaneous malignant melanoma

BACKGROUND. Increased activity of the protease cathepsin B has been demonst rated in many tumor cells. A correlation of cathepsin B activity and metast atic potential of melanoma has been well established. METHODS. The cathepsins B, D, H, and L were evaluated in normal skin, nevi, and melanoma samples to obtain information about their role and their regu lation in melanoma. The authors localized specific proteolytic activity wit h histochemistry, cathepsin protein immunohistochemistry, and mRNA with in situ hybridization. RESULTS. Activities and immunoreactivities of the cathepsins B and L were f ound to be increased in all melanocytic lesions. However, the staining for the corresponding mRNA levels was elevated only in melanomas. Cathepsin D p rotein and mRNA were expressed to a higher degree only in the dysplastic ne vus and in melanomas. The increase was due to tumor cells and cells of the surrounding tissue. Cathepsin H activity, immunoreactivity, and mRNA appear ed to be correlated inversely with the invasive potential of the lesion. CONCLUSIONS. It map be relevant for the malignant potential of the lesion w hether the increase in activity is accompanied by an increase in the mRNA l evel, Two different mechanisms-the existence of different mRNAs and the hig her transcription rate of the cathepsin gene-have been proposed for the reg ulation of cathepsin B activity in tumor cells. The current data suggest th at, depending on the thickness of the melanoma, cathepsin activity is regul ated by different mechanisms. The up-regulation of cathepsin gene transcrip tion appears to be characteristic for more invasive tumor cells. (C) 2001 A merican Cancer Society.