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

Abstract

BACKGROUND Increased activity of the protease cathepsin B has been demonstrated in many tumor cells. A correlation of cathepsin B activity and metastatic 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 regulation in melanoma. The authors localized specific proteolytic activity with histochemistry, cathepsin protein immunohistochemistry, and mRNA with in situ hybridization. RESULTS Activities and immunoreactivities of the cathepsins B and L were found to be increased in all melanocytic lesions. However, the staining for the corresponding mRNA levels was elevated only in melanomas. Cathepsin D protein and mRNA were expressed to a higher degree only in the dysplastic nevus and in melanomas. The increase was due to tumor cells and cells of the surrounding tissue. Cathepsin H activity, immunoreactivity, and mRNA appeared to be correlated inversely with the invasive potential of the lesion. CONCLUSIONS It may be relevant for the malignant potential of the lesion whether the increase in activity is accompanied by an increase in the mRNA level. Two different mechanisms—the existence of different mRNAs and the higher transcription rate of the cathepsin gene—have been proposed for the regulation of cathepsin B activity in tumor cells. The current data suggest that, depending on the thickness of the melanoma, cathepsin activity is regulated by different mechanisms. The up‐regulation of cathepsin gene transcription appears to be characteristic for more invasive tumor cells. Cancer 2001;91:972–82. © 2001 American Cancer Society.

Increased expression of Cathepsin B in oral squamous cell carcinoma

“…Additional processing of active CB generates the active two-chain form containing a heavy chain of 27-29 kDa and a light chain of 4-6 kDa 11,18,20 . Although, the precise mechanism is not clear, the functions of CTSB include lysosomal function, intracellular protein degradation, cell growth and biosynthesis of some peptide hormones, it is also found, in experimental studies, to be associated with more aggressive behaviour and metastatic potential 6,7,29,35 . CTSB has been implicated in the progression of various human tumours, and increased CTSB expression has also been found in many types of cancers, including OSCC.…”

Gene expression profiling and clinical outcome in melanoma: in search of novel prognostic factors

“…Cathepsins play important roles in the capacity of tumors to progress and to metastasize. Recently, an unfavorable prognostic effect of high cathepsin B and H serum levels with regard to survival was found in patients with advanced (stage II and III) melanoma, but this could not be confirmed on immunohistochemistry [30].…”

Autophagic-lysosomal dysregulation downstream of cathepsin B inactivation in human skin fibroblasts exposed to UVA

“…8-10 Importantly, molecular changes affecting cathepsins have been identified as causative factors in various skin pathologies such as tumorigenesis and inflammatory dysregulation. 11-14 …”