Expression of cathepsin B and cystatin C in human colorectal cancer

Hirai, Kyoji; Yokoyama, Munehiro; Asano, Gorō; Tanaka, Shigeo

doi:10.1016/s0046-8177(99)90094-1

Cited by 78 publications

(44 citation statements)

References 25 publications

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“…Downregulation of cystatin C gene was found in large granular lymphocyte leukaemia (Kothapalli et al, 2003). On the contrary, in squamous-cell lung cancer, no alteration in cystatin C protein level was described in matched pairs of normal and tumour tissue homogenates (Ebert et al, 1997;K epela et al, 1998) and, in colorectal cancer, a similar cystatin C mRNA level was found in cancerous and noncancerous tissue, which tended to show an inverse correlation with the cathepsin B levels (Hirai et al, 1999). The possibility of a similar number of pairs with equally increased and decreased cystatin C mRNA or protein level in these studies, resulting in the same average, could not be excluded.…”

Section: Discussionmentioning

confidence: 97%

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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Section: Discussionmentioning

confidence: 97%

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

et al. 2004

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“…Several enzyme systems participate in the degradation of ECM and basement membrane (Liotta et al, 1991), among which is cathepsin B, a lysosomal cysteine proteinase (Lah and Kos, 1998). Increased or altered expression of cathepsin B occurs in many types of tumors, including those of the breast (Foekens et al, 1998;Maguire et al, 1998), colon (Hirai et al, 1999;Iacobuzio-Donahue et al, 1997), prostate (Sinha et al, 1998) and lung (Werle et al, 1999), suggesting that cathepsin B may be involved in tumor invasiveness and metastasis. It has also been demonstrated that cathepsin B not only degrades components of the ECM such as laminin, collagen, and ®bronectin and structures of basement membranes (Buck et al, 1992), but also activates other proteolytic enzyme systems (Kobayshi et al, 1993;Schmitt et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells

et al. 2001

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Increases in abundance of cathepsin B transcript and protein correlate with increases in tumor grade and alterations in subcellular localization and activity of cathepsin B. The enzyme is able to degrade the components of the extracellular matrix (ECM) and activate other proteases capable of degrading ECM. To investigate the role played by this protease in the invasion of brain tumor cells, we transfected SNB19 human glioblastoma cells with a plasmid containing cathepsin B cDNA in antisense orientation. Control cells were transfected with vector alone. Clones expressing antisense cathepsin B cDNA exhibited signi®cant reductions in cathepsin B mRNA, enzyme activity and protein compared to controls. Matrigel Invasion assay showed that the antisense-transfected cells had a markedly diminished invasiveness compared with controls. When tumor spheroids containing antisense transfected SNB19 cells expressing reduced cathepsin B were co-cultured with fetal rat brain aggregates, invasion of fetal rat brain aggregates was signi®cantly reduced. Green Fluorescent Protein (GFP) expressing parental cells and antisense transfectants were generated for detection in mouse brain tissue without any postchemical treatment. Intracerebral injection of SNB19 stable antisense transfectants resulted in reduced tumor formation in nude mice. These results strongly support a role for cathepsin B in the invasiveness of human glioblastoma cells and suggest cathepsin B antisense may prove useful in cancer therapy. Oncogene (2001) 20, 3665 ± 3673.

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“…12 In addition, an immunostaining study demonstrated a significantly higher percentage of CatB-positive cases in a group of patients with liver metastases than in a group without. 13 In other studies, by contrast, significantly lower protein levels of CatB and CatL have been found in Dukes D stage tumors than in Dukes A and B stages. 11 Furthermore, whereas the tumor-to-normal ratios of CatB and CatL activities were not found to be increased in Dukes D stage, these ratios were significantly increased in other stages.…”

Section: Discussionmentioning

confidence: 79%

“…To our knowledge to date, many studies have investigated the correlation between levels of lysosmal proteases and clinical features of colorectal carcinoma by various methods, including examination of enzyme activity, 5,6,9,10,14,17 antigen, 10,12,16,17 and mRNA 7,13 in tissue homogenates and immunostaining 8,13,15,16,18 of the enzyme. The outcomes, among studies using different methods and also among those using the same method, have been conflicting.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] In colorectal carcinoma, many studies have shown that lysosomal proteases (cathepsins) are implicated in disease progression, metastasis, and the prognosis of patients. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] In the present study, which was concerned with the identification of the genes implicated in colorectal carcinoma metastasis, we performed subtraction cloning and isolated a clone corresponding to CLN2 (ceroid lipofuscinosis, neuronal 2). CLN2 encodes a lysosomal protease with tripeptidyl peptidase activity and a defect in this activity is associated with the late infantile neuronal ceroid lipofuscinosis (LINCL).…”

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confidence: 99%

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Overexpression in colorectal carcinoma of two lysosomal enzymes, CLN2 and CLN1, involved in neuronal ceroid lipofuscinosis

Tsukamoto

Iida

Dobashi

et al. 2006

Cancer

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The volume change, ΔVh,, accompanying the hydrophobic hydration associated with the volume phase transition in Poly(N‐isopropylacrylamide) gels was measured by a simple method. The hydration accompanies a negative ΔVh′−2.5 cm3/mol. The P‐T phase diagram, the coexistence curve, for the gels was determined from the swelling ratio‐pressure curves up to 350 MPa for various constant temperatures. The contour of the coexistence curve is shaped like an ellipsoid on the P‐T plain, which is a feature peculiar to the reversible pressure‐temperature denaturation of a protein. The thermodynamic analysis of the Clausius–Clapeyron relation for the measured ΔVh elucidates that the obtained coexistence curve represents the phase boundary between thermodynamic different phases like the two phases, native and denatured, of a protein and gives the transition enthalpy, ΔH, 5.2kJ/mol by estimate, which well coincides with the transition heat measured by a calorimetric method. Considering the volume‐dependent free energy, Δvmi · P, for the mixing free energy of the gel, we can fit the calculated curve to the measured swelling ratio‐pressure curve of PNIPA gels. The value of Δvmi changes the sign from negative to positive above around 100MPa. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 405–412, 2005

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Expression of cathepsin B and cystatin C in human colorectal cancer

Cited by 78 publications

References 25 publications

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

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

Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells

Overexpression in colorectal carcinoma of two lysosomal enzymes, CLN2 and CLN1, involved in neuronal ceroid lipofuscinosis

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