Prognostic impact of Cathepsin B and matrix metalloproteinase-9 in pulmonary adenocarcinomas by immunohistochemical study

Fujise, Naoki; Nanashima, Atsushi; Taniguchi, Yoshihiro; Matsuo, Seiichiro; Hatano, Kazuhiko; Matsumoto, Yoshihiro; Tagawa, Yutaka; Ayabe, Hiroyoshi

doi:10.1016/s0169-5002(99)00088-4

Cited by 54 publications

(27 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 89%

“…Retrospective immunohistochemical analysis revealed that patients who had cath B-positive tumors are characterized by a significantly shorter survival compared to patients who had cath B-negative tumor tissues (4). Moreover, results of another study showed that lung cancer patients with an up-regulation of cath B tended to have higher rates of haematogenous and intrapulmonary metastases (15). 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.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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: 89%

Section: Discussionmentioning

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

View full text Add to dashboard Cite

show abstract

“…Increased MMP-9 signal in both tumour and stromal cells has been shown to correlate with tumour aggressiveness in some carcinomas [8,21]. However, in spite of studies performed with lung carcinomas, the relationship of MMP-9 with clinicopathological variables is unclear [22,23,25,26,32]. This prompted us to study the expression of MMP-7 and MMP-9 in a large clinical cohort of patients with resected NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…In the previous studies of lung carcinomas usually no correlation between the expression of MMP-9 in tumour cells and clinicopathological factors has been found [22,23,32,[38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Expression of matrix metalloproteinases 7 and 9 in non-small cell lung cancer

et al. 2006

View full text Add to dashboard Cite

“…Among them, TIMP-1 has a selective binding with the pro-MMP-9 and is considered the main inhibitor for MMP-9 [13,15]. The detection of MMP9 expression has been performed in lung cancer by immunohistochemistry [1,7,[15][16][17][18][19], zymography [9,10,18,20], immunoenzymatic assays [21] and Northern analysis [8,15]. Increased plasma levels of MMP-9 protein were also detected in lung cancer patients [22,23].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung cancers by multiplex real time RT-PCR

et al. 2004

View full text Add to dashboard Cite

Summary Extracellular matrix (ECM) homeostasis is strictly maintained by a coordinated balance between the expression of matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs). Our study was focused on the simultaneous measurement of the expression profile of MMP9 mRNA and its principal inhibitor, TIMP-1, in 100 non small cell lung cancers (NSCLC) and in corresponding adjacent non malignant tissues. The measurement was performed with a multiplex quantitative RT-PCR assay based on TaqMan assay, using two probes labelled with different fluorocromes. We found that both MMP9 and TIMP-1 mRNAs were significantly higher in NSCLC (P < 0.0001) in comparison to corresponding controls as well as the MMP9/TIMP-1 ratio (P = 0.014). MMP9 and TIMP-1 mRNA expression was highly correlated in cancer samples (r = 0.73, P < 0.0001). The analysis in the two main histotypes revealed a significant increase of MMP9 mRNA in adenocarcinomas in comparison to normal tissues (P = 0.006) but not in squamous cell carcinomas, while TIMP-1 mRNA showed a significative increase both in adenocarcinomas and in squamous cell carcinoma samples (P = 0.02 and 0.01, respectively). Both MMP9 and TIMP-1 mRNAs were significantly correlated to lymphnode invasion and cancer stage. Survival analysis revealed that high levels of expression of MMP9 mRNA, but not of TIMP-1, were significantly associated to an unfavourable outcome in NSCLC patients in toto (P = 0.017). In addition our results showed that high levels of MMP9 expression are of independent prognostic impact in operable NSCLC.Our data seem to demonstrate a simultaneous and coordinated up-regulation of MMP9 and TIMP-1 expression at the mRNA level in NSCLC, even if this phenomenon seems variable according to the histotype. In addition, the increase of MMP9/TIMP-1 ratio may reflect an unbalance of their production in affected tissues. The increased expression of the two mRNAs, even not necessarily equate their enzymatic activities, seems to parallel a major cancer aggressiveness.

show abstract

Prognostic impact of Cathepsin B and matrix metalloproteinase-9 in pulmonary adenocarcinomas by immunohistochemical study

Cited by 54 publications

References 15 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

Expression of matrix metalloproteinases 7 and 9 in non-small cell lung cancer

Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung cancers by multiplex real time RT-PCR

Contact Info

Product

Resources

About