Lysosomal Proteases Cathepsins D, B, H, L and Their Inhibitors Stefins A and B in Head and Neck Cancer

Kos, Janko; Šmid, Alojz; Krašovec, Marta; Svetic, Branka; Lenarčič, Brigita; Vrhovec, Ivan; Škrk, Janez; Türk, Vito

doi:10.1515/bchm3.1995.376.7.401

Cited by 77 publications

(37 citation statements)

References 16 publications

(14 reference statements)

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“…A similar observation has been reported for head and neck carcinoma (Kos et al, 1995;Budihna et al, 1996) with 0.42 times lower Cath H levels in tumour tissue than in controls.…”

Section: Discussionsupporting

confidence: 88%

“…Higher levels were also found in tumour tissue and sera of patients with breast cancer (Gabrijelc ic et al, 1992) and in sera of melanoma patients . However, in head and neck tumours the levels of Cath H were lower in tumour tissue when compared to adjacent control tissue (Kos et al, 1995). Moreover, the lower levels of Cath H were associated with shorter disease-free survival period (Budihna et al, 1996).…”

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confidence: 97%

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Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

et al. 2000

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Summary In order to evaluate the role of cysteine peptidase cathepsin H (Cath H) in human lung cancer its protein levels were determined in 148 pairs of lung tumour tissue and adjacent non-tumourous lung parenchyma using the enzyme-linked immunosorbent assay technique. Additionally, Cath H levels were determined in sera of 171 patients with malignant tumours, 34 patients with benign lung diseases and 47 healthy controls. The median level of Cath H in tumour tissue was 0.64 times that in the corresponding lung parenchyma. Relating tumour levels with histological type we found higher Cath H levels in small-cell and adenocarcinomas and lower levels in squamous cell carcinoma, large-cell carcinoma and secondary tumours. A significant difference in Cath H level between lung tumour tissue and non-tumourous lung parenchyma was associated with the group of cigarette smokers (156 vs 263 ng mg -1 protein, P < 0.001). For this group of patients Cath H tumour levels correlated with the survival rate, while for the entire patient population this was not the case. Smokers with high tumour levels of Cath H experienced poor survival. Cath H was significantly higher in sera of patients with malignant and benign lung diseases than in control sera (P < 0.001). The increase was significant for all histological types, being the highest in small-cell and squamous cell carcinomas. Our study reveals that in lung tumours there is different behaviour of Cath H compared with other cysteine peptidases, e.g. cathepsin B and cathepsin L. Variations between tissue and serum levels of Cath H indicate either reduced expression or enhanced secretion of this enzyme in lung tumours.

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“…A similar observation has been reported for head and neck carcinoma (Kos et al, 1995;Budihna et al, 1996) with 0.42 times lower Cath H levels in tumour tissue than in controls.…”

Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 97%

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

et al. 2000

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“…Antigen levels were measured by using the enzymelinked immunoadsorbent assay (ELISA) based on the sandwich principle as previously described (11). Measurements of cath B, cath L, cystatin C, u-PA and u-PAR in the sera using ELISA were performed according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Detection of cathepsin B, cathepsin L, cystatin C, urokinase plasminogen activator and urokinase plasminogen activator receptor in the sera of lung cancer patients

Chen

Fei

et al. 2011

Oncology Letters

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Abstract. The present study aimed to determine the levels of cathepsin B (cath B), cathepsin L (cath L), cystatin C, urokinase plasminogen activator (u-PA) and urokinase plasminogen activator receptor (u-PAR) in the sera of patients with lung cancer compared to healthy controls using ELISA. Concomitantly, the relationship between the components and clinicopathological prognosis was analyzed. The study included 30 healthy volunteers and 105 lung cancer patients. Blood samples were collected and cath B, cath L, cystatin C, u-PA and u-PAR measurements were made using ELISA. Results showed that the levels of cath B, cath L, cystatin C, u-PA and u-PAR were significantly higher in the patient group compared to the healthy controls. The significance was marked for cath B and mild for u-PAR in correlation with lymph node metastasis. There was no significance for other parameters. Notably, patients with a combination of high cystatin C and high cath B levels had significantly lower survival probability as compared to those with cystatin C + /cath B -or with cystatin C -/cath B -. Similarly, patients with a combination of high u-PA and u-PAR experienced significantly shorter survival. Furthermore, the univariate analysis revealed that cath B, u-PAR, lymph node metastases, stage and grade were related to survival. However, findings of the multivariate Cox analysis indicated that the sera levels of cath B, u-PAR and lymph node metastases may serve as independent prognostic variables in patients with lung cancer. IntroductionCathepsins are members of the lysosomal cysteine proteases family and are usually located inside a lysosome. Numerous studies showed a correlation of increased proteolytic activity of cysteine cathepsins with neoplastic transformation, tumor invasion and metastasis through the destruction of extracellular matrix components and basement membranes in tumor spread. Cathepsin B (cath B) is able to activate pro-urokinasetype plasminogen activator and enhance subsequent plasmin generation. Increased levels of cath B and L were observed in tissues of primary and metastatic tumors in a number of cancer types (1-3). The serum level of cath B may serve as a prognostic factor for patients with advanced melanoma. By contrast, the serum level of cath L was not statistically different in the control, non-metastatic and metastatic patient groups (3). Moreover, using immunohistochemical analysis, the overexpression of cath B and L was shown to correlate with more aggressive tumor behavior, early relapse and shorter survival (2). However, in lung cancer tissue, cath L did not reveal any association with prognosis (4).Cystatin C, an accurate marker of glomerular filtration rate and endogenous cysteine protease inhibitor, has been found in a variety of human tissues, but is mainly found in extracellular body fluid and serum. Increased levels of cystatin C in tumor tissues were shown to correlate with a favourable prognosis of cancer patients (5), whereas higher levels of cystatin C in body fluids have been associated with ...

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“…3 Patients without extension of tumor tissue beyond nodal capsule and those with pN 0 -stage of disease were included. 4 Oral cavity, oropharynx, hypopharynx. HR, Hazard ratio; CI, Confidence interval.…”

Section: Tissue Homogenate (Cytosol)mentioning

confidence: 99%

Cysteine cathepsins and stefins in head and neck cancer: an update of clinical studies

Strojan¹

2008

Radiology and Oncology

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tract, major salivary glands and nodes from the neck. The majority of tumors is of squamous cell origin and alcohol and tobacco abuse are the two most important etiological factors. Surgery and radiotherapy are standard treatment options with systemic therapy being added to irradiation of the patients with increased risk for disease recurrence. 1 To distinguish biologically more aggressive and less aggressive head and neck carcinomas within each traditional risk-category, numerous new prognostic factors were evaluated on genetic, mRNA or protein levels. Among the factors that promote tumor growth and invasion, several protease Radiol Oncol 2008; 42(2): 69-81. doi:10.2478/v10019-008-0006-4

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Lysosomal Proteases Cathepsins D, B, H, L and Their Inhibitors Stefins A and B in Head and Neck Cancer

Cited by 77 publications

References 16 publications

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking

Detection of cathepsin B, cathepsin L, cystatin C, urokinase plasminogen activator and urokinase plasminogen activator receptor in the sera of lung cancer patients

Cysteine cathepsins and stefins in head and neck cancer: an update of clinical studies

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