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

Cordes, Colja; Bartling, Babett; Simm, Andreas; Afar, Dany; Lautenschläger, Christine; Hansen, Gesine; Silber, Rolf-Edgar; Burdach, Stefan; Hofmann, Hans‐Stefan

doi:10.1016/j.lungcan.2008.07.005

Cited by 33 publications

(22 citation statements)

References 28 publications

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“…This finding is consistent with the immunohistochemical study of Cordes et al (17), which showed the weakest expression and staining intensity for cath L in lung cancer among the cathepsins. These findings support the hypothesis that the role of cath L in lung cancer progression and metastasis is less important than that proposed for other tumors (15).…”

Section: Discussionsupporting

confidence: 93%

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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Section: Discussionsupporting

confidence: 93%

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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“…15 Cathepsin K is over-expressed as well as secreted by malignant tumour cells, and several studies showed that CTSK was expressed by the stromal cells closely associated with the tumour. [3][4][5][6][7] We also observed that CTSK was significantly expressed in the peritumoral 16 The present study demonstrated a marked CTSK expression in the stromal fibroblasts of all types of SCCs, which was in sharp contrast to the benign and pre-malignant specimens. In SCC, stromal cell-derived CTSK could play an important role in promoting the invasive growth of SCCs, considering its absence in SK, AK, KA, and most BD, which has already been postulated in other malignancies.…”

Section: Discussionsupporting

confidence: 53%

“…6 A high expression level of CTSK together with cathepsin B significantly correlated with shorter recurrence-free and overall survival in pulmonary adenocarcinomas. 7 Therefore, CTSK could be a marker for the aggressive biological behaviour of tumours. To our knowledge, there is only one published study that evaluated CTSK expression in four cases of cutaneous squamous cell carcinoma (SCC).…”

Section: Introductionmentioning

confidence: 99%

Stromal expression of cathepsin K in squamous cell carcinoma

Yan

Takahara

Xie

et al. 2011

Acad Dermatol Venereol

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“…Cathepsin K is expressed in the stroma of basal cell and squamous cell carcinomas, especially in invasive cases, but not in normal fibroblasts 31 . A high expression level of cathepsin K together with cathepsin B is significantly correlated with shorter recurrence-free interval and overall survival time in pulmonary adenocarcinomas 32 .…”

Section: Invasion Ecm and Cancer-associat-ed Fibroblastsmentioning

confidence: 95%

Epithelial Tumor, Invasion and Stroma

Furue

2011

Ann Dermatol

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

Cited by 33 publications

References 28 publications

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

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

Stromal expression of cathepsin K in squamous cell carcinoma

Epithelial Tumor, Invasion and Stroma

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