Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-five surgical specimens of malignant human prostate, 3 lymph nodes with metastatic prostate carcinoma, 11 normal human prostates, as well as 3 human prostate cell lines (DU-145, PC3 and LNCaP) were examined for the expression of the human matrix metalloproteinase-7 gene (MMP-7) from the human collagenase family (originally called PUMP-1 for putative metalloproteinase-1) [Quantin et al. (1989) Biochemistry 28:5327-5334; Muller et al. (1988) Biochem J 253:187-192; Matrisian and Bowden (1990) Semin Cancer Biol 1:107-115]. Northern blots were prepared using total RNA extracted from 18 prostate adenocarcinomas, 2 lymph nodes with metastatic prostate carcinoma and 11 normal human prostates. When the northern blots were hybridized with a 32P-labeled MMP-7 cDNA probe, a 1.2-kb mRNA was detected in 14 out of 18 prostate adenocarcinomas, 1 out of 2 metastatic lymph nodes, and 3 out of 11 normal prostates. The 3 human prostate cell lines did not show any evidence of the MMP-7 transcript. In situ hybridization was conducted to localize the MMP-7 mRNA to individual cells using a 35S-labeled MMP-7 cRNA. In situ hybridization was carried out on snap-frozen tissue sections of 7 prostate adenocarcinomas and 3 lymph nodes containing metastatic prostate adenocarcinoma using the same tissues previously probed by northern analysis as well as new samples. In situ hybridization revealed that the MMP-7 gene was expressed in the epithelial cells of primary prostate adenocarcinoma as well as in invasive and metastatic cells. MMP-7 expression was also seen focally in some dysplastic glands but not in stroma. Additional northern blot analysis was performed using probes to human type-IV collagenase, type-I collagenase and stromelysin I in human prostate adenocarcinoma as well as normal prostate tissue. Our results indicated that 6 out of 10 adenocarcinoma samples and none of the 4 normal samples were positive for type-IV collagenase transcripts. Tissue samples were also examined for the expression of type-I collagenase (9 adenocarcinomas and 4 normal) and stromelysin I (13 adenocarcinomas) by northern analysis. None of the tissues was found to express the transcripts of interest at detectable levels. These data suggest that certain metalloproteinases are present in prostatic adenocarcinoma and may play a role in invasion and metastasis.
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PMID:Expression of metalloproteinase genes in human prostate cancer. 184 60

We have systematically analyzed the proliferative properties of the clonogenic cells of the R3327 transplantable rat prostate adenocarcinoma (colony forming units, prostatic adenocarcinoma, CFU-PA). Pronase was determined to be more effective than either trypsin or collagenase in obtaining the largest number of viable cells from a solid R3327 tumor. Digestion with 2.5 mg/ml yielded a maximum of 5.6 X 10(4) CFU-PA/g of tumor tissue, with higher concentrations resulting in s substantially lower fraction of CFU-PA while producing larger overall cell yields. Bacto-agar at 0.35% supported the growth of the largest number of CFU-PA and was sharply concentration dependent with concentrations greater than 0.4% completely suppressing CFU-PA growth. The addition of conditioned medium (CM) from R3327 liquid cell cultures to agar cultures resulted in a specific twofold increase in CFU-PA/10(4) cells, whereas CM from R3327A cells was less effective and CM from rat skin fibroblasts least stimulatory. The addition of washed rat red blood cells (RBC) either within the agar culture itself or in an overlayer was highly stimulatory, resulting in as much as a fivefold increase in CFU-PA to 6 to 8 x 10(4)/g.
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PMID:Proliferative properties of the clonogenic cells of the R3327 prostate adenocarcinoma. 633 74

At present, there is no established diagnostic method by which the metastatic ability of an individual prostatic cancer can be accurately predicted. Metastasis is a multistep process, the first critical step of which is invasion. Tumor invasion has been suggested to involve a variety of hydrolytic enzyme activities; therefore, the tumor levels of these activities might be indicative of the overall metastatic ability of the cancer. In order to evaluate if the quantitative levels of hydrolytic enzymes can be used to predict the metastatic ability of individual prostatic cancers, five different Dunning R-3327 rat prostatic adenocarcinoma sublines, with widely varying metastatic abilities, were assayed for the respective levels of a variety of hydrolytic enzyme activities (collagenase, trypsin-like, cathepsin B, neutral protease, N-acetyl-beta-glucosaminidase, chymotrypsin-like, leucine aminopeptidase, elastase, and plasminogen activator). These studies demonstrated that most hydrolytic activities are not elevated when going from normal prostate to prostatic cancer. In addition, only the levels of elastase and chymotrypsin-like activity were found to be consistently higher in highly metastatic prostatic cancers than in either the normal prostate or low-metastatic prostatic cancers. It was found that, by combining the relative activities of elastase and chymotrypsin-like activity and then dividing by the relative activities of N-acetyl-beta-glucosaminidase, a biochemical metastatic index could be constructed which accurately reflected the respective metastatic ability of the Dunning sublines.
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PMID:Biochemical methods for predicting metastatic ability of prostatic cancer utilizing the dunning R-3327 rat prostatic adenocarcinoma system as a model. 653 99

Procedures are described for the isolation and cultivation of normal rat prostatic epithelial cells. The techniques, which involve collagenase digestion and Ficoll purification of the epithelial population, are efficient, inexpensive, and produce pure monolayers. Included is a scanning and transmission electron microscopic study comparing cells isolated in vitro to rat prostatic epithelial cells in situ. Further ultrastructural comparisons are made to a malignant cell line, the Dunning R3327H Copenhagen rat prostatic adenocarcinoma.
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PMID:Isolation, in vitro cultivation, and electron microscopy of normal and malignant prostatic epithelial cells from the Copenhagen rat. 742 94

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC-E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.
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PMID:Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma. 960 Mar 41

Diagnostic and prognostic markers for prostatic cancer (PCa) include conventional protein markers (e.g., PAP, PSA, PSMA, PIP, OA-519, Ki-67, PCNA, TF, collagenase, and TIMP 1), angiogenesis indicator (e.g., factor VIII), neuroendocrine differentiation status, adhesion molecules (E-cadherin, integrin), bone matrix degrading products (e.g., ICPT), as well as molecular markers (e.g., PSA, PSMA, p53, 12-LOX, and MSI). Currently, only PSA is used clinically for early diagnosis and monitoring of PCa. The histological differential diagnosis of prostatic adenocarcinoma includes normal tissues such as Cowper's gland, paraganglion tissue and seminal vesicle or ejaculatory duct as well as pathological conditions such as atypical adenomatous hyperplasia, atrophy, basal cell hyperplasia and sclerosing adenosis. A common PCa is characterized by a remarkable heterogeneity in terms of its differentiation, microscopic growth patterns and biological aggressiveness. Most PCa are multifocal with signi ficant variations in tumor grade between anatomically separated tumor foci. The Gleason grading system which recognizes five major grades defined by patterns of neoplastic growth has gained almost uniform acceptance. In predicting the biologic behavior of PCa clinical and pathological stages are used as the major prognostic indicators. Among the cell proliferation and death regulators androgens are critical survival factors for normal prostate epithelial cells as well as for the androgen-dependent human prostatic cancer cells. The androgen ablation has been shown to increase the apoptotic index in prostatic cancer patients and castration also promotes apoptotic death of human prostate carcinoma grown in mice. The progression of PCa, similarly to other malignancies, is a multistep process, accompanied by genetic and epigenetic changes, involving phenomenons as adhesion, invasion and angiogenesis (without prostate specific features).
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PMID:Prostate Cancer - Old Problems and New Approaches. (Part II. Diagnostic and Prognostic Markers, Pathology and Biological Aspects). 1117 6

Collagenous micronodules, also known as mucinous fibroplasia, are microscopic structures characterized by the presence of small eosinophilic nodules in areas immediately adjacent to prostatic glandular epithelium. The pathogenesis of collagenous micronodules is unknown, although their relation with mucin has been suggested. The objective of our study was to analyze the structural characteristics of collagenous micronodules by using histochemistry, immunohistochemistry, and electron microscopy to elucidate the pathogenesis of this lesion. We analyzed 15 cases of prostate adenocarcinoma (12 prostatectomy specimens and 3 biopsy specimens) with collagenous micronodules. The collagenous micronodules were closely associated with well-formed malignant glands, where tumor cells exhibited basophilic to amphophilic cytoplasm. Occasionally, intraluminal collagen fragments were observed within malignant but not benign glands. Collagenous micronodules were not associated with mucin, confirmed by negative stainings of mucicarmin or alcian blue in all the collagenous micronodules analyzed in this study. Therefore, the term "mucinous fibroplasia" may not be accurate. Collagenous micronodules stained weakly positive for periodic acid-Schiff. Trichrome stain highlighted the presence of collagenous micronodules as distinct blue structures. Collagen IV and laminin immunostaining performed in 12 cases outlined the micronodules with minimal staining in the center. These findings indicated that collagenous micronodules consisted of predominantly collagen fragments admixed with basement membrane material. Ultrastructurally, they were composed of fragmented banded collagen fibrils surrounded by the basement membrane material. Collagenous micronodules are formed by subepithelial accumulations of fragmented collagen fibers, possibly related to the digestion by collagenase produced by prostatic adenocarcinoma cells.
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PMID:Pathogenesis and significance of collagenous micronodules of the prostate. 1261 Mar 51