Cathepsin B in infiltrated lymph nodes is of prognostic significance for patients with nonsmall cell lung carcinoma

Werle, Bernd; Kraft, Clemens; Lah, Tamara T.; Kos, Janko; Schanzenbächer, Ulrike; Kayser, Klaus; Ébert, W.; Spieß, Eberhard

doi:10.1002/1097-0142(20001201)89:11<2282::aid-cncr17>3.0.co;2-4

Cited by 42 publications

(18 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One reason for this poor prognosis may be the high concentration of cath B at the periphery of the tumor cell foci, indicating that these areas were possibly involved in the process of tumor cell invasion. In addition, a significant increase of the cath B activity in tumor-infiltrated lymph nodes was observed compared to non-infiltrated regional lymph nodes, which also impaired patient survival (16). Consistent with these data, results of our study showed that the levels of cath B were significantly increased in the sera of lung cancer patients as compared to those in healthy controls.…”

Section: Discussionsupporting

confidence: 90%

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

View full text Add to dashboard Cite

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 ...

show abstract

Section: Discussionsupporting

confidence: 90%

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

View full text Add to dashboard Cite

show abstract

“…Moreover, the enzyme activity of Cathepsin B was 4.5-fold higher in lung tumor tissue compared with lung parenchyma [7]. Sukoh et al and Kayser et al performed retrospective immunohistochemical analysis showing that patients who had Cathepsin B-positive tumors are characterized by a significantly shorter overall survival compared to patients who had Cathepsin B-negative tumor tissues [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…One reason explaining this poor prognosis might be the high concentration of Cathepsin B at the periphery of the tumor cell foci [28], indicating that these areas were possibly involved in the process of tumor cell invasion. In addition, Werle et al showed a significant increase of the Cathepsin B activity in tumor infiltrated lymph nodes compared to non-infiltrated regional lymph nodes, which also impaired the overall survival of the patients [7].…”

Section: Discussionmentioning

confidence: 99%

“…Although former studies revealed an association between Cathepsin B levels in tumors and poor prognosis of the NSCLC patients [5][6][7], the identification of high-risk patients by analyzing only one Cathepsin at a time might be of limited value. Therefore, we examined the expression of all members of the Cathepsin family by DNA-array techniques to determine an appropriate Cathepsin or a group of appropriate Cathepsins, which might be highly significant for the patients' prognosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2009

View full text Add to dashboard Cite

“…5 Many primary lung tumors contain significantly higher levels of cathepsin B protein and express higher levels of cathepsin B activity than the adjacent lung parenchyma, with high levels correlating to a worse prognosis. 22,23 In lung tumors that do not overexpress cathepsin B directly or from host response, the benefits of probe activation in tumor detection will likely be diminished. An additional confounding factor is the protease overexpression in areas of inflammation, which may increase the background signal.…”

Section: Discussionmentioning

confidence: 99%

Near infrared thoracoscopy of tumoral protease activity for improved detection of peripheral lung cancer

Figueiredo

Alencar

Weissleder

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

Improvement in tumor detection using ''smart'' probes in combination with microcatheter fluorescence thoracoscopy was evaluated in a mouse model. These imaging probes increase in fluorescence intensity after protease activation; cathepsin B is a major activator of the probes used in this study. Lewis lung carcinoma cells were orthotopically implanted in the subpleural lung parenchyma. Two activatable near infrared (NIR) probes with different excitation and emission wavelength were administered intravenously to determine whether wavelength would modulate target to background ratio (TBR). Mice were selectively intubated and thoracoscopy performed. A 0.8 mm outer diameter imaging catheter was used to record simultaneous white-light (anatomic) and NIR (protease expression) images. At both wavelength pairs evaluated (680/700 and 750/780 nm excitation/emission), the intrinsic luminosity differences between tumors and normal lung in uninjected animals was low (p > 0.3 and p 5 0.4, respectively and TBR near 1). In mice receiving protease probes IV, tumors were significantly more fluorescent than adjacent lung (p < 0.0005 for 680/700 and p < 0.006 for 750/780) and TBR increased to approximately 9-fold. Confirmatory fluorescence microscopy and immunohistochemistry were similar and revealed that normal lung had very low levels when compared to tumors of cathepsin B and probe fluorescence. In conclusion, protease sensitive imaging probes selective for cathepsin B, imaged with NIR microcatheters, significantly increase the TBR, making small peripheral lung tumors more readily apparent. Such an approach may be a useful adjunct in staging or restaging patients with lung cancer to find minimal disease in the pleural and subpleural space. ' 2005 Wiley-Liss, Inc.

show abstract

Cathepsin B in infiltrated lymph nodes is of prognostic significance for patients with nonsmall cell lung carcinoma

Cited by 42 publications

References 19 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

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

Near infrared thoracoscopy of tumoral protease activity for improved detection of peripheral lung cancer

Contact Info

Product

Resources

About