Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density

Lösch, Alexander; Schindl, Monika; Kohlberger, Petra; Lahodny, J.; Breitenecker, G.; Horvat, Reinhard; Birner, Peter

doi:10.1016/j.ygyno.2003.11.016

Cited by 53 publications

(51 citation statements)

References 30 publications

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“…The protein product of the CTSD gene was selected for this purpose because of the availability of a commercial antibody and prior studies implicating this protease in the pathogenesis of several cancers, including ovarian and breast (16,17). Using a semiquantitative immunohistochemical scoring system, chemosensitive samples displayed significantly higher CTSD protein expression than the chemoresistant samples (Fig.…”

Section: Resultsmentioning

confidence: 99%

Gene Expression Profiles Associated with Response to Chemotherapy in Epithelial Ovarian Cancers

Jazaeri¹,

Awtrey

Chandramouli³

et al. 2005

Clinical Cancer Research

177

106

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Purpose: The goal of this study was to determine whether distinct gene expression profiles are associated with intrinsic and/or acquired chemoresistance in epithelial ovarian carcinoma. Experimental Design: Gene expression profiles were generated from 21primary chemosensitive tumors and 24 primary chemoresistant tumors using cDNA-based microarrays. Gene expression profiles of both groups of primary tumors were then compared with those of 15 ovarian carcinomas obtained following platinum-based chemotherapy (''postchemotherapy'' tumors). A theme discovery tool was used to identify functional categories of genes involved in drug resistance. Conclusions: These data show that gene expression profiling can discriminate primary chemoresistant from primary chemosensitive ovarian cancers. Gene expression profiles were also identified that correlate with states of intrinsic and acquired chemoresistance and that represent targets for future investigation and potential therapeutic interventions.

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Section: Resultsmentioning

confidence: 99%

Gene Expression Profiles Associated with Response to Chemotherapy in Epithelial Ovarian Cancers

Jazaeri¹,

Awtrey

Chandramouli³

et al. 2005

Clinical Cancer Research

177

106

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“…Some reports revealed increased cathepsin D activity in serum and/or tumor homogenates, especially in malignancies [32]. Strong cathepsin D immunoexpression was found in nasopharyngeal [33], oral [34], gastric [35], colorectal [31], renal [36], breast [37] and ovarian [38] carcinomas. In our study, positive cathepsin D staining in cancer cells was found in slightly more than half of the ESCCs cases.…”

Section: Discussionmentioning

confidence: 99%

“…In submucosal colorectal carcinoma, a positive stromal reaction was associated with lymph node metastasis [31]. However, surprisingly, it was an independent prognostic factor for prolonged disease-free survival in invasive ovarian cancers [38]. Cathepsin K-positive fibroblasts and tumorassociated macrophages were found in aggressive histological types of lung adenocarcinoma (acinar/papillary and mixed type) [13] and in ductal breast carcinoma [10].…”

Section: Discussionmentioning

confidence: 99%

Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma.

Szumiło

Burdan²,

Zinkiewicz³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:The key features of malignant neoplasms are their local invasiveness and metastatic potential. Syndecan-1 -integral membrane heparan sulfate proteoglycan and cathepsins D and K -lysosomal proteases are important factors influencing different aspects of these processes. The study was undertaken to determine their expression in esophageal squamous cell carcinoma, and analyze relationship to selected clinicopathological features as well as to survival. Formalin-fixed, paraffin-embedded sections from 39 advanced esophageal squamous cell carcinoma were used for immunohistochemical staining. The epithelial and stromal staining were evaluated separately and compared to conventional clinicopathological features and one-year survival. Positive epithelial immunostaining for syndecan-1, cathepsin D and K were observed in 82.05%, 56.41% and 30.77% of tumors, respectively. However, stromal staining was noted in 51.28%, 51.28% and 46.15% ones, respectively. Epithelial syndecan-1-positive cases were significantly more frequent in well-and moderately differentiated carcinomas. Stromal cathepsin D expression predominated in tumors with infiltrative growth pattern. However, there were no statistically significant differences between any marker-positive and -negative groups with respect to other clinicopathological features studied. The only factors significantly influencing one-year survival were epithelial cathepsin D staining and distant metastasis. In a group of patients who survived one year post surgery, the percentage of cases with negative epithelial cathepsin D staining and without features of distant metastasis were higher. The results may suggest a relationship between syndecan-1 and cathepsins D and K with growth and invasiveness of esophageal squamous cell carcinoma, but such thesis requires further study on a larger and more heterogeneous population.

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“…Stromal CD expression correlated with microvessel density in ovarian tumors [207]. Significant association between CD expression of host stromal cells and vascular density was described in breast cancer tumours [208].…”

Section: Angiogenesismentioning

confidence: 90%

Cathepsin D—Many functions of one aspartic protease

Beneš

Větvička

Fusek

2008

Critical Reviews in Oncology/Hematology

540

474

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For years, it has been held that cathepsin D (CD) is involved in rather nonspecific protein degradation in a strongly acidic milieu of lysosomes. Studies with CD knock-out mice revealed that CD is not necessary for embryonal development but it is indispensable for postnatal tissue homeostasis. Mutation that abolishes CD enzymatic activity causes neuronal ceroid lipofuscinosis (NCL) characterized by severe neurodegeneration, developmental regression, visual loss and epilepsy in both animals and humans.In the last decade, however, an increasing number of studies demonstrated that enzymatic function of CD is not restricted solely to acidic milieu of lysosomes with important consequences in regulation of apoptosis. In addition to CD enzymatic activity, it has been shown that apoptosis is also regulated by catalytically inactive mutants of CD which suggests that CD interacts with other important molecules and influences cell signaling.Moreover, procathepsin D, secreted from cancer cells, acts as a mitogen on both cancer and stromal cells and stimulates their pro-invasive and pro-metastatic properties. Numerous studies found that pCD/CD level represents an independent prognostic factor in a variety of cancers and is therefore considered to be a potential target of anti-cancer therapy.Studies dealing with functions of cathepsin D are complicated by the fact that there are several simultaneous forms of CD in a cell -pCD, intermediate enzymatically active CD and mature heavy and light chain CD. It became evident that these forms may differently regulate the above mentioned processes.In this article, we review the possible functions of CD and its various forms in cells and organisms during physiological and pathological conditions.

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Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density

Cited by 53 publications

References 30 publications

Gene Expression Profiles Associated with Response to Chemotherapy in Epithelial Ovarian Cancers

Gene Expression Profiles Associated with Response to Chemotherapy in Epithelial Ovarian Cancers

Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma.

Cathepsin D—Many functions of one aspartic protease

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