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)

Six patients with liver metastases from carcinoid or colon carcinoma underwent hepatic derterialization. This operation, known to cause both tumor necrosis and liver cell damage, caused considerable increases of several lysosomal acid hydrolases in the circulation. Thus, beta-glucosidase showed a small temporary increase during the operation, followed by a slower but higher reaction reaching a maximum 12 to 36 hours postoperatively. Similar reactions were noted for beta-glucuronidase, acid phosphatase, beta-galactosidase, arylsuphatase A, and N-acetyl-beta-glucosaminidase while no reactions were found for cathepsin D. Very high enzyme levels occurred in a patient dying from bleeding complications in the postoperative period.
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PMID:Plasma activities of lysosomal enzymes after hepatic dearterialization in man. 0 1

We made an effort to identify a reliable source for obtaining large quantities of both free (PSA) and PSA-ACT complex for the preparation of the calibrator for the PSA assay. Using size exclusion chromatography, we found both free PSA and PSA-ACT complex in the conditioned cell medium of the LNCaP cell line, which was derived from a human metastatic adenocarcinoma of the prostate. An assay specific for PSA-ACT reacted only with the PSA-ACT complex from cells grown in serum-free medium, and not with the complex from the cell medium grown in 10% calf serum. We also found both free PSA and PSA-ACT complex in 15% of cytosols prepared from breast tumor tissues; the cytosol PSA concentrations ranged from 0.1 to 110 ng/ml. No correlation was found between cytosol PSA and concentrations of estrogen receptor, progestin receptor, epidermal growth factor receptor, cathepsin D, or the ectodomain of c-erbB-2 protein. Based on chromatographic characterizations and the slope of their dose-response curves, it appears that both free PSA and PSA-ACT complex found in the cytosols are similar to PSA complex from the cell medium and the serum of prostate cancer patients. Ectopic PSA was also detected in pooled sera from patients with breast, ovarian, pancreatic, and colon carcinoma. The PSA concentrations in these serum pools increased with the level of their dominant tumor marker. In any event, the LNCaP cell medium appears to be a reliable source for obtaining both free and ACT-complexed PSA of human tumor origin for the preparation of PSA assay calibrators.
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PMID:PSA immunoreactivity detected in LNCaP cell medium, breast tumor cytosol, and female serum. 756 42

We have studied the cellular content and the extracellular release of cathepsins B and D, and of plasminogen activator, in 2 different tumor cell populations before confluence and after late confluence: the HT-29 colon carcinoma cell line, which contains primarily undifferentiated cells, and a subpopulation derived from this cell line, which contains cells committed to differentiation into mucus-secreting goblet cells after confluence. In both populations, cellular cathepsin-B activity increased after confluence, and latent cathepsin B was found in all culture media. In the parental cell line, cellular cathepsin D activity decreased after confluence; however, cathepsin D was secreted at high levels into the extracellular medium. In contrast, in the subpopulation of cells committed to differentiation, cellular cathepsin D activity increased after confluence, and cathepsin D was not secreted into the extracellular medium, but was immunolocalized in the apical brush border of the differentiated cells. Plasminogen activator of urokinase type was identified by immunocytochemistry. Both subconfluent cell populations, and the post-confluent undifferentiated cell population, produced plasminogen activator activity at similar levels. In contrast, in the differentiated postconfluent cells, the production of plasminogen activator activity was markedly lower. Our data show that the differentiation of HT-29 colon carcinoma cells into mucus-secreting cells impairs the secretion of plasminogen activator and cathepsin D, but does not affect cathepsin B.
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PMID:The state of differentiation of HT-29 colon carcinoma cells alters the secretion of cathepsin D and of plasminogen activator. 791 58

We have studied the intracellular trafficking of cathepsin D in different colon carcinoma cell populations: the HT-29 cell line, composed of >95% undifferentiated cells; 2 subpopulations derived from this cell line, containing cells committed to differentiation into mucin-secreting cells (HT-29 MTX) or enterocyte-like cells (HT-29 G-) after confluence; and the Caco-2 cell line, which spontaneously differentiates into enterocyte-like cells after confluence. Post-confluent undifferentiated HT-29 cells and differentiated enterocyte-like HT-29 G- and Caco-2 cells secrete significant levels of cathepsin D in culture medium, in contrast to post-confluent differentiated mucin-secreting HT-29 MTX cells, which secrete this enzyme at a very low level. The intracellular content and the mRNA level of cathepsin D increase after confluence in the different cell types, particularly in Caco-2 cells, which intensify the secretion of cathepsin D along with the differentiation process post-confluence. Membrane-associated mature cathepsin D was detected in HT-29 cells but not in Caco-2 cells. In the different types of cell, pro-cathepsin D associates with the membrane concomitantly to its binding to an Mr 72,000 protein. Membrane association persists after dissociation of the complex in HT-29 cells but not in Caco-2 cells. In the mucin-secreting HT-29 MTX cells, cathepsin D was immunolocalised to the membrane of mucin vacuoles localised under the brush border. Our results show that cathepsin D can be regulated differently in colon carcinoma cells, and this finding might have specific functional implications for each cell type.
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PMID:Regulation of cathepsin D dependent on the phenotype of colon carcinoma cells. 894 19

In the present work, we analyzed the variations in the expression and trafficking of cathepsin D (CD), a lysosomal endopeptidase, associated with the enterocytic differentiation of the human colon carcinoma HT-29 cell line. In spite of the fact that the abundance of CD mRNA was severalfold higher in undifferentiated HT-29 cells than in their enterocyte-like differentiated counterparts, the intracellular levels of CD activity and protein were found to be much higher in the latter. The kinetic of transport of newly synthesized proCD was different in the two cell populations: (a) full conversion of proCD into the lysosomal mature form required more than 24 h in differentiated cells, whereas it was almost complete within 8 h in undifferentiated HT-29 cells; and (b) the extracellular release of proCD was shown to occur more rapidly and to a higher degree in undifferentiated than in differentiated cells. Most of the secreted proCD contained phosphomannoses. Secretion of beta-hexosaminidase activity doubled, whereas that of CD activity was unchanged, upon vacuolar alkalinization with ammonium chloride or chloroquine. Inhibition of the lysosomal-autophagic degradative pathway resulted in the accumulation of proCD molecules in undifferentiated HT-29 cells. Altogether these data suggest that: (a) the expression and the posttranslational fate of CD in HT-29 colon cancer cells are largely affected by the state of their enterocytic differentiation; and (b) in this cell line the acid-dependent mannose 6-phosphate receptor pathway is, at best, little involved in the trafficking of CD.
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PMID:Expression and posttranslational fate of cathepsin D in HT-29 tumor cells depend on their enterocytic differentiation state. 930 Jan 84

A case of an aggressive desmoid tumor in a patient with familial adenomatous polyposis is described. The lesion rapidlyenlarged with compression of adjacent structures including the ureter and small bowel, and the patient died because of small bowel perforation and hydronephrosis 3 years after detection of small desmoid tumors at the time of a prophylactic coloproctectomy for a colon carcinoma. Immunohistochemically, proliferating cell nuclear antigen (PCNA), p21WAF1/CIP1 and cathepsin D indices, but not the bcl-2 index, which were defined as the numbers of immunoreactive tumor cells per 1000 tumor cells, increased in line with tumor progression. The tumor did not show staining for collagen IV, but was characterized by intense staining for basic fibroblast growth factor (bFGF). Accordingly, tumor aggression was related to increases in both cell proliferation and protease activity, as well as an enhanced expression of bFGF. In addition, the desmoid tumor showed deregulation between PCNA and p21WAF1/CIP1 because the normal inverse relation between these two was not apparent.
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PMID:An aggressive desmoid tumor in a patient with familial adenomatous polyposis: immunohistochemical findings. 1002 64

Hypoxia-inducible factor 1 (HIF-1) transactivates genes the products of which mediate tumor angiogenesis and glycolytic metabolism. Overexpression of the HIF-1 alpha subunit, resulting from intratumoral hypoxia and genetic alterations, has been demonstrated in common human cancers and is correlated with tumor angiogenesis and patient mortality. Here we demonstrate that hypoxia or HIF-1 alpha overexpression stimulates Matrigel invasion by HCT116 human colon carcinoma cells, whereas this process is inhibited by a small interfering RNA directed against HIF-1 alpha. We show that HIF-1 regulates the expression of genes encoding cathepsin D; matrix metalloproteinase 2; urokinase plasminogen activator receptor (uPAR); fibronectin 1; keratins 14, 18, and 19; vimentin; transforming growth factor alpha; and autocrine motility factor, which are proteins that play established roles in the pathophysiology of invasion. Neutralizing antibodies against uPAR block tumor cell invasion induced by hypoxia or HIF-1 alpha overexpression. These results provide a molecular basis for promotion of the invasive cancer phenotype by hypoxia and/or HIF-1 alpha overexpression.
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PMID:Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. 1261 33