Cystatins and Cathepsins in Breast Carcinoma

Abstract

The increased expression of proteolytic systems is one of the characteristics of transformed and malignant cells and their evaluations in whole tumor homogenates were considered as possible diagnostic and/or prognostic factors. Abnormal intracellular distribution, increased activities and secretion of cysteine proteinases (CPs) cathepsin B (Cat B) and L (Cat L), were associated with tumor progression. In the present study of matched pairs of breast carcinoma and normal breast tissue, the activities of Cat B and Cat L in breast carcinoma homogenates were found to be 20 and 50 fold higher, respectively, than in normal tissues. In contrast, a decrease in total inhibitory activity of cysteine proteinase inhibitors (CPIs) was observed but an average ratio between tumor and normal tissues was only 0.75. One of the CPIs, stefin A, was also determined immunochemically. The activities of CPs and CPIs were compared to the increased levels of cathepsin D (Cat D) activities in individual patients, but no statistically significant correlations were found.We correlated CPs and CPIs with morphological and receptor data as well as the axilliary lymph node metastases. There was no statistical correlation of CP and CPIs with the number of lymph node metastases. However, highly elevated levels of Cat B and Cat L and lowered CPI activities in tumor cytosols were often associated with poorly differentiated carcinomas and those with negative ER and PR values. We conclude that cysteine-dependent proteolysis may play an important role in breast tumors.

Cystatin C – A Fast and Reliable Biomarker for Glomerular Filtration Rate in Head and Neck Cancer Patients

“…While one report showed increased levels of serum cystatin C in HNC patients when compared to healthy controls [35], suggesting a pathological role of cystatin C in HNC, another investigation demonstrated that high levels of cystatin C in tumor tissue had a protective effect, being associated with prolonged survival [32]. Similar results were published for breast [15,16] and lung cancer [11].…”

Simultaneous expression of Cathepsins B and K in pulmonary adenocarcinomas and squamous cell carcinomas predicts poor recurrence-free and overall survival

“…Beside lung carcinoma [13], increased levels of Cathepsin have also been found in breast carcinoma [14,15], colon carcinoma [16], head and neck carcinoma [17], oesophageal carcinoma [18] and glioma [19,20] as well as in the sera of tumor patients [19][20][21][22][23][24]. Moreover, the enzyme activity of Cathepsin B was 4.5-fold higher in lung tumor tissue compared with lung parenchyma [7].…”

Functional expression of recombinant human stefin A in mammalian and bacterial cells

“…More compelling evidence demonstrated continual decrease in the level of stefin A mRNA during the progression of murine skin papillomas to carcinoma (12). Similarly, decreased stefin A transcripts were observed in 4 of 5 breast carcinomas as compared to matched normal breast tissues (13). In addition to decreased amounts of stefin A in malignant tissues, Lah and coworkers (14,15) have shown that stefin A, isolated from human sarcoma tissue, has an altered inhibitory activity, being less effective than normal stefin A in inhibiting the proteolytic activity of both papain and cathepsin B. Lastly, we have demonstrated in murine tumors that there is an overall decrease of CPI activity accompanied with an enrichment of the activity within the plasma membrane fraction (16).…”