Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cathepsin D, a lysosomal protease, was examined by immunohistochemistry in 481 breast carcinomas. The immunoreactivity for cathepsin D was registered in the tumour cells, in the surrounding stroma, and in the macrophages and correlated with clinicopathological parameters. In univariate analysis of survival data, less than 25% positive tumour cells, any positivity in the stroma, and moderate or strong positivity in the macrophages were poor prognostic parameters. In multivariate analysis, all three parameters were of independent prognostic significance; therefore a cathepsin D index was constructed. In multivariate analysis the cathepsin D index was also found to be of independent poor prognostic significance both in patients with and without lymph node metastases. Progesterone receptor status was an independent prognostic parameter in patients with lymph node metastases. From the present study we concluded that the cathepsin D index was a independent poor prognostic parameter.
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PMID:The prognostic-significance of cathepsin-d in breast carcinomas - an immunohistochemical study. 2160 42

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers largely due to disseminated disease at the time of presentation. Here, we investigated the role and mechanism of action of the metastasis-associated protein anterior gradient 2 (AGR2) in the pathogenesis of pancreatic cancer. AGR2 was induced in all sporadic and familial pancreatic intraepithelial precursor lesions (PanIN), PDACs, circulating tumor cells, and metastases studied. Confocal microscopy and flow cytometric analyses indicated that AGR2 localized to the endoplasmic reticulum (ER) and the external surface of tumor cells. Furthermore, induction of AGR2 in tumor cells regulated the expression of several ER chaperones (PDI, CALU, RCN1), proteins of the ubiquitin-proteasome degradation pathway (HIP2, PSMB2, PSMA3, PSMC3, and PSMB4), and lysosomal proteases [cathepsin B (CTSB) and cathepsin D (CTSD)], in addition to promoting the secretion of the precursor form pro-CTSD. Importantly, the invasiveness of pancreatic cancer cells was proportional to the level of AGR2 expression. Functional downstream targets of the proinvasive activity of AGR2 included CTSB and CTSD in vitro, and AGR2, CTSB, and CTSD were essential for the dissemination of pancreatic cancer cells in vivo. Taken together, the results suggest that AGR2 promotes dissemination of pancreatic cancer and that its cell surface targeting may permit new strategies for early detection as well as therapeutic management.
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PMID:AGR2 is a novel surface antigen that promotes the dissemination of pancreatic cancer cells through regulation of cathepsins B and D. 2194 70

Despite recent advances in surgical techniques and therapeutic treatments, survival from colorectal cancer (CRC) remains disappointing with some 40-50% of newly diagnosed patients ultimately dying of metastatic disease. Current staging by light microscopy alone is not sufficiently predictive of prognosis and would benefit from additional support from biomarkers in order to stratify patients appropriately for adjuvant therapy. We have identified that cathepsin D expression was significantly greater in cells from invasive front (IF) area and liver metastasis (LM) than those from main tumour body (MTB). Cathepsin D expression was subsequently examined by immunohistochemistry in tissue microarrays from 119 patients with CRC. Strong expression in tumour cells at the IF did not correlate significantly with any clinico-pathological parameters examined or patient survival. However, cathepsin D expression in cells from the MTB was highly elevated in late stage CRC and showed significant correlation with subsequent distant metastasis and shorter cancer-specific survival. We also found that macrophages surrounding tumour cells stained strongly for cathepsin D but there was no significant correlation found between cathepsin D in macrophages at IF and MTB of CRC patient with the clinic-pathological parameters examined.
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PMID:Cathepsin D Expression in Colorectal Cancer: From Proteomic Discovery through Validation Using Western Blotting, Immunohistochemistry, and Tissue Microarrays. 2291 86

Cathepsin D is a protease involved in the metastasis and angiogenesis of mammary carcinomas. This review analyzes the significance of the tumor protease cathepsin D in mammary carcinomas as a tumor marker. We present a systematic overview based on a selective Medline search. Cathepsin D is expressed in mammary carcinomas and exhibits higher expression in invasive ductal carcinomas compared with lobular carcinomas. Nodal positive carcinomas showed reduced cathepsin D expression compared to lymph node metastases, and increased expression has been observed in hormone-receptor negative tumors. Thus, the expression of cathepsin varies between the two histological types. Increased cathepsin-D expression in acinar affection has also been described. The lack of an association of cathepsin D with known prognostic factors such as CA15-3, ERalpha and ERbeta does not prevent it from being using as a tumor marker. Cathepsin has already been used along with other genes as a prognostic parameter for carcinoma patients in gene arrays.
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PMID:Significance of the tumor protease cathepsin D for the biology of breast cancer. 2426 19

Epithelial ovarian cancer (EOC) metastasis to the omentum requires implantation and angiogenesis. We propose that prometastatic changes in the omental endothelium (for angiogenesis) and mesothelium (for implantation) are critical. We investigated the expression of angiogenic proteases [cathepsin D (CD), cathepsin L (CL), and matrix metalloproteinase 2 (MMP2) and MMP9] and vascular endothelial growth factor A (VEGFA) in the mesothelium and endothelium of omentum from patients with EOC with omental metastases and control patients with benign ovarian tumors. Endothelial expression of CL, VEGFA, and MMP9 and mesothelial expression of VEGFA, MMP9, and CD were significantly increased in patients with metastasized EOC. High expression of MMP9 and VEGFA in endothelium and mesothelium and CD in mesothelium was positively associated with poor disease-specific survival (DSS). High MMP9 expression in either endothelium or mesothelium and presence of ascites prospectively showed the greatest risk of shorter DSS [hazard ratio (HR)= 6.16, 95% confidence interval (CI) = 1.76-21.6, P = .0045; HR = 11.42, 95% CI = 2.59-50.35, P = .0013; and HR = 6.35, 95% CI = 2.01-20.1, P = .002, respectively]. High endothelial MMP9 expression and ascites were independent predictors of reduced DSS and overall survival, together resulting in worst patient prognosis. Our data show that omental metastasis of EOC is associated with increased proangiogenic protein expression in the omental endothelium and mesothelium.
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PMID:Clinical Relevance of Increased Endothelial and Mesothelial Expression of Proangiogenic Proteases and VEGFA in the Omentum of Patients with Metastatic Ovarian High-Grade Serous Carcinoma. 2491 75

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and has a poor prognosis due to relatively unspecific early symptoms, and thus often advanced stage, metastasized cancer at presentation. Metastasis of EOC occurs primarily through the transcoelomic route whereby exfoliated tumor cells disseminate within the abdominal cavity, particularly to the omentum. Primary and metastatic tumor growth requires a pool of proangiogenic factors in the microenvironment which propagate new vasculature in the growing cancer. Recent evidence suggests that proangiogenic factors other than the widely known, potent angiogenic factor vascular endothelial growth factor may mediate growth and metastasis of ovarian cancer. In this review we examine the role of some of these alternative factors, specifically cathepsin D and cathepsin L.
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PMID:The Potential Role of the Proteases Cathepsin D and Cathepsin L in the Progression and Metastasis of Epithelial Ovarian Cancer. 2661 May 86

Metastasis, which involves the spread of cancer cells to distant tissues and organs, is a major cause of cancer-associated mortality. Although the use of anesthetics and analgesics may affect cancer cell metastasis, the underlying molecular mechanism remains unclear. Autophagy is a lysosome-based dynamic intracellular catabolic process that serves a crucial role in cancer cell metastasis. In order to investigate the role of autophagy in the migration of cancer cells treated with analgesics, immunofluorescence, western blotting, wound healing assay and cell invasion assay were performed in the present study. The results from immunofluorescence and western blotting demonstrated that the opioid analgesic sufentanil stimulated LC3 induction in NCI-H460 cells. Furthermore, sufentanil increased LC3 and Beclin1 protein levels, but inhibited the fusion of autophagosomes and lysosomes. In addition, sufentanil decreased cathepsin D protein level and increased p62 protein level. The addition of chloroquine (CQ) to sufentanil did not induce a further increase in LC3-II protein levels in NCI-H460 cells, suggesting the impairment of autophagic degradation. Furthermore, treatment with trehalose stimulated the migration of sufentanil-treated cells, whereas additional treatment with CQ did not further decrease the migration of sufentanil-treated cells. In addition, sufentanil co-treatment with trehalose significantly increased the invasion of lung cancer cells, whereas, additional treatment with CQ did not further reduce the invasion of sufentanil-treated cells. These results indicated that autophagy may be involved in the inhibition of NCI-H460 cell migration by sufentanil, and that sufentanil may be considered as a favorable analgesic for patients with lung cancer.
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PMID:Sufentanil impairs autophagic degradation and inhibits cell migration in NCI-H460 in vitro. 3178 26


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