Cathepsin B/Cystatin C Complex Levels in Sera from Patients with Lung and Colorectal Cancer

Abstract

A sandwich-type ELISA has been developed for quantification of the complex between the cysteine proteinase cathepsin B (CB) and its reversible tight-binding inhibitor cystatin C (CC) in normal and pathological sera. The assay is based on a combination of catching Ab (3E1), raised against CB, and a horseradish peroxidase-labelled detection Ab (1A2), raised against CC. Only the CB/CC complex is able to evoke a signal in this assay. The detection limit of the assay was 15.5 nM and the working range between 31.3-200 nM. The within and between-run coefficients of variance (CV) varied from 4.7% to 9.4% and 11% to 12.8%, respectively, demonstrating satisfactory reproducibility of the method. The concentration of the CB/CC complex was determined in sera from 90 healthy controls, 32 patients with non-cancerous lung diseases, 148 patients with lung and 32 patients with colorectal cancer. The CB/CC complex was significantly less abundant in sera of patients bearing malignant lung tumours than in those with non-cancerous lung diseases or healthy controls (p<0.001). In colorectal cancer sera its level was significantly lower in advanced stages C and D than in early Dukes' stages A and B (p=0.02). Our results show that the increased levels of CB in malignant sera are not impaired effectively by CC and support the hypothesis of hindered inhibitory capability during cancer progression.

Cathepsin B, Cathepsin H, Cathepsin X and Cystatin C in Sera of Patients with Early-Stage and Inflammatory Breast Cancer

“…In line with this finding, previous studies have reported a positive correlation between serum cathepsin B expression and disease progression in various cancer types (23,25,27,(30)(31)(32). Only few and conflicting data have been published on the relation of serum cathepsin H expression to cancer prognosis and its role in tumor progression and metastasis is still not well understood (23,29,33).…”

Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis

“…In lung tumour tissue, cathepsin B was found to be more resistant to inactivation by E-64 than cathepsin B from control lung tissue (Křepela et al, 1995). Furthermore, it has been shown that the serum level of cathepsin B/cystatin C complexes was significantly decreased in patients with malignant lung tumours than in healthy controls (Zore et al, 2001). Additionally, higher total concentrations of cystatin C found in sera of patients with lung, colorectal and melanoma cancer (Kos and Lah, 1998) suggested enhanced secretion of cystatin C from tumour cells, increasing at the same time the intracellular proteolytic potential of cysteine proteases.…”

Serum Cystatin C and Emphysema: Results from the National Health and Nutrition Examination Survey (NHANES)

“…The increase in the concentration of cystatins as a maker of tissue destruction has been utilized in several diseases. In the current literature, CysC has been studied extensively in kidney disease, cardiovascular disease, and solid organ malignancy [12][13][14][15][16][17][18][19][20][21]. CysC has been studied as a more sensitive marker for renal dysfunction than serum creatinine [15,16].…”

“…It has been suggested that CysC may more accurately estimate glomerular filtration rate (GFR) than creatinine, particularly in the setting of the elderly and those with mild renal insufficiency [15,16]. Furthermore, it has been postulated that CysC plays a role in pathogenesis of malignancy and metastasis [17][18][19][20][21]. Cathepsins B and L and their potent inhibitor CysC have been studied in the pathogenesis of multiple pulmonary processes, including bronchiectasis [22], lung malignancy [23], and pleural effusions [24].…”