Expression of Cysteine Proteinases Cathepsins B and K and of Cysteine Proteinase Inhibitor Cystatin C in Giant Cell Tumor of Tendon Sheath

Hansen, Torsten; Pk, Petrow; Gäumann, Andreas; Gm, Keyszer; Otto, Mike; Kirkpatrick, Charles James; Kriegsmann, Jörg

doi:10.1038/modpathol.3880309

Cited by 14 publications

(12 citation statements)

References 30 publications

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“…However, several studies indicate a predominant expression of cathepsin K in osteoclasts and osteoclast-like giant cells (12,14,15,(31)(32)(33)(34). In the present study, staining of this proteinase was strong in osteoclasts at sites of bone destruction and in multinucleated giant cells of the perimatrix, whereas only few mononuclear cells in this region were detected.…”

Section: Discussioncontrasting

confidence: 51%

“…Microscopic evaluation of the slides was performed according to previously described methods (15). Cell types were monitored as nonaffected chondrocytes, surrounding connective tissue, and external ear canal skin (NT); keratinized squamous cholesteatoma epithelium, i.e., matrix ( …”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Deficiency of cathepsin K results in pyknodysostosis, an autosomal recessive osteochondrodysplasia (11). Expression of cathepsin K has been demonstrated in sev-eral chronic inflammatory lesions associated with bone destruction such as osteomyelitis (12), rheumatoid arthritis (13), osteoarthritis (14), nodular tenosynovitis (15), and aseptic hip prosthesis loosening (16). In addition, specific exogenous inhibitors of cathepsin K have been shown to decrease the destruction of bone significantly (17).…”

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confidence: 99%

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Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

et al. 2001

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Cholesteatoma is a nonneoplastic lesion of the middle ear space or mastoid that is histologically characterized by a progressive bone erosion of the ossicles and surrounding bone. Several matrixdegrading enzymes have been implicated as mediators of this bone erosion. Because the novel cysteine proteinase cathepsin K has been shown to play a central role in bone resorption, we examined the expression of this enzyme in tissue specimens of cholesteatoma. Tissue specimens of 9 patients with cholesteatoma were obtained during middle-ear surgery. Expression of cathepsin K mRNA was determined by RT-PCR using specific primers. Immunohistochemical analysis of cathepsin K protein expression in tissue sections was performed by using the streptavidin-alkaline phosphatase technique. Expression of both cathepsin K mRNA and protein was detected in areas affected by cholesteatoma, whereas specimens of nonaffected ear cartilage and surrounding tissue were not positive. In addition, cathepsin K was detected in numerous multinucleated giant cells, particularly osteoclasts at the site of bone degradation. In contrast, keratinized squamous epithelium was negative for cathepsin K. These data demonstrate that the matrix-degrading cysteine proteinase cathepsin K may be involved in bone erosion in cholesteatoma. Strong expression of this collagenolytic enzyme in osteoclasts suggests that these cells are mainly involved in cathepsin K-mediated bone destruction.

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Section: Discussioncontrasting

confidence: 51%

Section: Immunohistochemistrymentioning

confidence: 99%

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confidence: 99%

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Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

et al. 2001

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“…Immunohistochemically, cystatin C protein was stained intracellularly in the cytoplasmic compartment of tumour cells in a variety of cancer types (Lignelid and Jacobsson, 1992;Lignelid et al, 1997;Yoshimura et al, 2000;Gaumann et al, 2001;Hansen et al, 2001;Yano et al, 2001). The mechanisms controlling the intracellular inhibition of cysteine proteinases in endosomes and lysosomes with cystatin C entering the endosomal -lysosomal pathway by endocytotic uptake may include dimerisation (Ekiel and Abrahamson, 1996;Merz et al, 1997), proteolytic fragmentation by cathepsin D (Lenarčič et al, 1991) or neutrophilic granulocyte elastase (Abrahamson et al, 1991).…”

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

et al. 2004

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To determine the role of the cysteine proteinase inhibitor cystatin C in the invasive behavior of squamous cell carcinoma of the head and neck (SCCHN), Cystatin C protein level was measured in 82 pairs of primary tumour tissue and adjacent noncancerous mucosa, using the enzyme-linked immunosorbent assay. The median level of cystatin C in tumour tissue was 1.18 times lower than that in corresponding mucosa (P ¼ 0.031). In normal mucosa samples, the cystatin C level was influenced by the site of sampling: it was lower in nonlaryngeal tissue samples (oral cavity, oro-or hypopharynx) than in laryngeal samples (P ¼ 0.004). The tumour cystatin C level correlated inversely with pN-stage (P ¼ 0.047), whereas a trend of lower cystatin C levels was observed in the group with extranodal tumour extension compared to those with no extranodal spread (P ¼ 0.069). In univariate analysis, the patients with low tumour cystatin C levels exhibited poor disease-free survival (DFS, P ¼ 0.013) and disease-specific survival (DSS, P ¼ 0.013). In multivariate analysis, the most powerful predictor of survival was pN-stage (DFS: P ¼ 0.040, HR 2.78; DSS: P ¼ 0.011, HR 4.36,), followed by the cystatin C level (DFS: P ¼ 0.043, HR 0.22; DSS: P ¼ 0.067, HR 0.25). When comparing the prognostic strength of cystatin C to that of stefin A, another cysteine proteinase inhibitor, which emerged as the most significant prognosticator for survival in our previous study analysing the same cohort of patients, stefin A proved to be significantly more reliable predictor for both DFS and DSS than cystatin C. Our results indicate that cystatin C is implicated in the invasive behavior of SCCHN, and that there are variations in regulation of proteolytic pathways under nonmalignant conditions, inherent to individual subsites inside the upper aerodigestive tract. The correlation between high cystatin C levels and improved survival concurs with the concept of the protective role of high levels of cysteine proteinase inhibitors in tissue homogenates that has been previously suggested by the survival results in breast and lung carcinoma as well as SCCHN.

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“…These are particularly found to destroy the proteins of the cellular matrix, such as collagen and lamina, and are therefore involved in the invasion and metastasis of some malignant tumors (13-16). numerous studies have reported that lysosomal cysteine protease cathepsin is highly expressed in human and murine tumor tissues (10,17,18) and sera (9). in certain studies, lysosomal cysteine protease cathepsin cdna was transferred into tumor cells, increasing tumor cell metastasis, while in other studies, lysosomal cysteine protease cathepsin genes were knocked out or rna interference technology was used for cysteine protease cathepsin genes (19-21), decreasing tumor cell invasion in matrigel in vitro, preventing solid tumor formation and inhibiting angiogenesis in a mouse model or in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of Cystatin C in human stomach neoplasms

et al. 2010

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Abstract. cystatin c is a member of the cysteine protease inhibitor family and functions to decrease protease production. a recent study showed that it is aberrantly expressed in many malignant tumors in association with tumor invasion and metastasis. our study aimed to detect cystatin c expression in stomach neoplasm tissues and adjacent reparative normal tissues. Samples of cancerous and non-cancerous stomach tissue were obtained via surgery as matched pairs from 12 patients with stomach neoplasms and preserved in paraffin. The expression of Cystatin C in the samples was investigated by immunohistochemistry. Fisher's exact test was used to analyze the relationship between stomach neoplasms and adjacent normal tissues. additionally, mrna was extracted and analysed by reverse transcriptase-polymerase chain reaction. The intensity of cystatin c immunostaining was increased in the tumor tissues compared to the adjacent normal tissues. cystatin c mrna expression was increased in stomach neoplasms compared to the normal tissues (p<0.05). The results indicate that the expression of cystatin c may serve as a marker for stomach neoplasms.

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Expression of Cysteine Proteinases Cathepsins B and K and of Cysteine Proteinase Inhibitor Cystatin C in Giant Cell Tumor of Tendon Sheath

Cited by 14 publications

References 30 publications

Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

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

Expression of Cystatin C in human stomach neoplasms

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