Proteases in gastrointestinal neoplastic diseases

Herszényi, László; Plebani, Mario; Carraro, Paolo; Paoli, Massimo De; Roveroni, Giovanni; Cardin, Romilda; Foschia, Francesca; Tulassay, Zsolt; Naccarato, R.; Farinati, Fabio

doi:10.1016/s0009-8981(99)00227-2

Cited by 52 publications

(41 citation statements)

References 56 publications

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“…Similarly, in the case of cathepsin B, the expression was most common in the intestinal type tumors infiltrating the whole gastric wall, but no statistically significant correlations were observed. However, we noted a strong statistically significant association between cathepsin B expression and lymph node involvement, which is consistent with other literature reports [29,30]. Cathepsin B expression is related to the histological grade and TNM stage [29].…”

Section: Discussionsupporting

confidence: 93%

The expression of matrix metalloproteinase 9 and cathepsin B in gastric carcinoma is associated with lymph node metastasis, but not with postoperative survival.

Czyżewska

Guzińska‐Ustymowicz²,

Kemonä³

et al. 2008

Folia Histochem Cytobiol.

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Degradation components of basement membrane could be crucial for tumor invasion. A key role in this process has been assigned to cysteine proteases, i.e. cathepsins and matrix metalloproteinases. The purpose of this study was to investigate the relationship of the expression of MMP-9 and cathepsin B with tumor aggressiveness expressed by lymph node metastases and survival rates in gastric carcinoma patients. Slides of 5 μm-thick serial sections from 91 patients with primary gastric carcinoma were prepared and analyzed for MMP-9 and cathepsin B expression using anti-human monoclonal antibody (NCL-MMP-9 clone; dilution 1:40 and NCL-CATH-B clone; dilution 1:40). The patients were clinically monitored for 84 months. We found no association between the expression of MMP-9 and cathepsin B in main mass of tumor and patients' gender, tumor location, Lauren's classification or histological differentiation. Also no correlation was observed between the expression of MMP-9 in main mass of tumor and depth of invasion. A strong statistically significant association was found between the expression of MMP-9 and cathepsin B in main mass of tumor and lymph node involvement (p<0.001; p<0.001, respectively). However, we observed no correlation between the expression of MMP-9 and cathepsin B in main mass of tumor and lymph node involvement or 5-year overall survival. Our results may suggest that the expression of matrix metalloproteinase-9 (MMP-9) and cathepsin B is correlated with lymph node metastasis in advanced gastric carcinoma, but not with patients' postoperative survival.

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Section: Discussionsupporting

confidence: 93%

The expression of matrix metalloproteinase 9 and cathepsin B in gastric carcinoma is associated with lymph node metastasis, but not with postoperative survival.

Czyżewska

Guzińska‐Ustymowicz²,

Kemonä³

et al. 2008

Folia Histochem Cytobiol.

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“…In particular, the last function is thought to be critical in conferring the invasiveness and metastatic potential of cancer cells (Hanahan and Weinberg, 2000). Indeed, this biological role of serine proteases seems to accord well with clinical reports which show that aberrant expression of serine proteases such as the plasminogen activator correlate positively with the invasiveness and metastasis, hence poor prognosis in different malignancies (Monsky et al, 1991;Powell et al, 1993;Herszenyi et al, 1999;Kuhn et al, 1999;Herszenyi et al, 2000).…”

mentioning

confidence: 66%

Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer

et al. 2001

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Summary Kallikrein gene 5 (KLK5, also known as KLK-L2), located on chromosome 19q13.4, is one of the newly identified members of the kallikrein gene family, which is a subgroup of the serine protease enzyme family. In normal human tissues, KLK5 is highly expressed in skin, mammary gland and testis. Preliminary RT-PCR analysis has indicated that KLK5 is expressed in a subset of ovarian tumours. We have thus hypothesized that KLK5 may be a new prognostic indicator in ovarian cancer. We have examined the mRNA expression of KLK5 in 142 malignant ovarian tissues. Tumours were pulverized, total RNA was extracted, and cDNA was prepared by reverse transcription. KLK5 was amplified by PCR using gene specific primers, and the identity of the PCR product was verified by sequencing. Ovarian tissues were then classified as KLK5 positive or negative, based on ethidium bromide staining of the PCR product on agarose gels. KLK5 was found to be highly expressed in 58/142 (41%) of ovarian cancer samples while its level of expression was very low in normal ovarian tissues. We found a strong positive relation between KLK5 expression and tumour grade (P = 0.006) and disease stage (P = 0.027). Univariate survival analysis revealed that patients with ovarian tumours positive for KLK5 expression had an increased risk for relapse and death (P = 0.018 and 0.022, respectively). In multivariate analysis, KLK5 expression showed independent prognostic value only in the subset of tumours with lower grade disease (grades I and II). We conclude that KLK5 expression is associated with more aggressive forms of epithelial ovarian carcinoma and has indepdent prognostic value in low grade tumours. 643-650 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1649, available online at http://www.idealibrary.com on http://www.bjcancer.comIn the present study, we have evaluated KLK5 mRNA expression in relation to patient survival and other clinicopathologic variables in epithelial ovarian carcinoma. Our results demonstrate that KLK5 is an independent prognostic marker of poor prognosis in a subset of patients with grade I/II tumours. MATERIALS AND METHODS Ovarian cancer specimens and patients142 consecutive patients with epithelial ovarian carcinoma were included in this study, with ages ranging from 25 to 80 with a median of 59 years. Patients underwent surgery and treatment for primary ovarian carcinoma at the Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, University of Turin, Turin, Italy between July, 1991 and April, 1999. Follow-up information (median follow-up period 48 months) was available for 138 patients, among whom 83 (60%) have relapsed and 55 (40%) died. Of the 142 ovarian adenocarcinomas, for which histological diagnosis was available, 64 (45%) were serous papillary, 26 (18%) endometrioid, 22 (16%) undifferentiated, 12 (8%) clear cell, 11 (8%) mucinous, 6 (4%) Mullerian and 1 (1%) was unclassified. Due to the relatively small sample size, the clear cell, mucinous and Mullerian types were combined into one category...

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“…Most gastric cancer cells secret urokinase-type plasminogen activator (u-PA) which converts latent TGFβ to active TGFβ [26,27]. The latent TGFβ from gastric fibroblasts and scirrhous gastric cancer cells may be activated by u-PA from scirrhous gastric cancer cells.…”

Section: Migration-stimulating Activity Of Gastric Cancer Cells By Fimentioning

confidence: 99%

Cancer–Stromal Interactions in Scirrhous Gastric Carcinoma

Yashiro

Hirakawa

2010

Cancer Microenvironment

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Fibroblasts play an important role in the progression, growth and spread of gastric cancers. Cancer-stroma interactions have been especially evident in the scirrhous type of gastric carcinoma. Fibroblasts are associated with the cancer progression at the primary and metastatic site. The proliferative and invasive ability of scirrhous gastric cancer cells are closely associated with the growth factors produced by organ-specific fibroblasts. Fibroblasts are therefore a key determinant in the malignant progression of gastric cancer and represent an important target for cancer therapies.

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Proteases in gastrointestinal neoplastic diseases

Cited by 52 publications

References 56 publications

The expression of matrix metalloproteinase 9 and cathepsin B in gastric carcinoma is associated with lymph node metastasis, but not with postoperative survival.

The expression of matrix metalloproteinase 9 and cathepsin B in gastric carcinoma is associated with lymph node metastasis, but not with postoperative survival.

Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer

Cancer–Stromal Interactions in Scirrhous Gastric Carcinoma

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