Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attempts to design an agent which would release cytotoxic nitrogen mustards within collagenase-producing tumors led to the synthesis of Cbz-L-Pro-L-Leu-Gly-L-Pro-Gly-NHC6H4N(CH2CH2Cl)2 (10). 10 was cleaved in vitro by bacterial and tumor-associated collagenase as expected at the peptide bond joining L-leucine and glycine to give Gly-L-Pro-Gly-NHC6H4N(CH2CH2Cl)2 which was over six times more toxic, on a molar basis, than 10. In vivo tests of 10 against well-advanced Sarcoma-180 gave disappointing results. The lack of specific antitumor activity may be accounted for by the presence of competing cleavage reactions by collagenases in certain normal tissues.
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PMID:Collagenase-sensitive peptidyl-nitrogen mustards as potential antitumor agents. 21 58

Three human malignant melanomas were cultured in pure populations and one tumor was cloned into melanotic and amelanotic cell lines. In the homogenates of these cultured cells, specific collagenase activities were demonstrated by isotope release from 14C-labeled collagen, disc electrophoresis, and specific cleavage of collagen molecules as demonstrated in the segment long spacing form. No significant collagenase activity was observed in the culture media. Interestingly, early cultures had a high collagenase activity in the cells and as they were successively subcultured, the activity diminished. Cysteine completely inhibited the degradation of tropocollagen as determined by disc electrophoresis and EDTA partially inhibited the degradation. It is concluded that human malignant melanoma cells produce a specific collagenase in vitro which can be extracted in early culture directly from the homogenate.
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PMID:Collagenolytic activities of cultured human malignant melanoma cells. 21 92

We estimated collagenolytic activity of 10 invasive carcinomas of the cervix by means of a biological assay. Collagenolysis was found in 7 specimens. In order to detect the origin of the collagenolytic enzyme additional inhibition studies with ethylendiaminetetraacetate and normal human serum were performed. Normal human serum inhibited the enzymatic process by a mean percentage of 14.9%, EDTA up to 9.1%. D-penicillamine and 1.10-o-phenanthroline which inhibit collagenase specifically stopped the enzymatic activity of the tumor completely. According to our results it can be suggested that the collagenolytic activity of carcinoma of the cervix uteri is not derived from serum or from polymorphonuclear cells but is created by the tumor itself.
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PMID:[Collagenolytic activity of cervix carcinoma]. 21 49

Antibodies to fibronectin and to distinct types of procollagens and collagens were used in immunofluorescent staining to localize these proteins in cell cultures. Normal human skin or lung fibroblasts produced a fibrillar pericellular matrix in which fibronectin and procollagen (types I and III) showed extensive codistribution. Fibronectin and procollagen were synthesized by the same cells as judged by double-stain immunofluorescence. Pericellular procollagen was specifically digested with collagenase without an effect on the fibrillar distribution of matrix fibronectin. Brief treatment with trypsin removed both matrix proteins. The human tumor cell lines HT-1080 (fibrosarcoma) and RD (rhabdomyosarcoma) produced little or no matrix fibronectin or procollagen. At sites of cell contact, simian virus 40-transformed lung fibroblasts (VA13) produced small amounts of pericellular fibrillar matrix fibronectin that codistributed with procollagen type I. Intracellular fibronectin and procollagen were visualized in all of these human sarcoma cell lines. When chicken embryo fibroblasts infected with a T class mutant (NY68) of Rous sarcoma virus temperature-sensitive for transformation were maintained at the nonpermissive temperature (41 degrees ) the cells had normal phenotype and a fibrillar matrix containing fibronectin and procollagen was present. At the permissive temperature (35 degrees ), the cells showed transformed phenotype and the matrix was lost. The failure to produce a pericellular fibronectin/collagen matrix may account for several phenotypic characteristics of transformed cultured fibroblasts.
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PMID:Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: fibronectin and procollagen. 21 6

The effect of the potent tumor promoter phorbol 12-myristate 13-acetate (PMA) on collagen synthesis, a differentiated property of chick embryo fibroblasts, was examined. Collagen synthesis, as measured by the rate of formation of [3H]hydroxyproline from [3H]proline, was found to be decreased in cells treated with PMA but not in cells treated with the parent alcohol phorbol. The decrease in collagenase-sensitive proteins was confirmed by polyacrylamide gel electrophoresis of cell lysates, indicating that the decrease could not be ascribed simply to an effect on prolyl hydroxylase. Although a decrease in collagen synthesis was observed after one day, five days were required for a maximal reduction to 20% of that of dimethyl sulfoxide-treated controls. The effect of PMA on collagen synthesis was reversible. It was therefore not the result of a permanent transformation of the cells or of the selection of a population of cells with a reduced capacity for collagen synthesis. Collagen synthesis was decreased in chick embryo fibroblasts transformed by Rous sarcoma virus. Treatment of these cells with PMA for 5 days brought about a further decrease to 50% of the level in dimethyl sulfoxide-treated transformed controls.
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PMID:Decrease in collagen production in normal and Rous sarcoma virus-transformed chick embryo fibroblasts induced by phorbol myristate acetate. 21 32

The specificity of human skin collagenase and of an enzyme from an invasive tumor were studied by using types I, II, III, IV, and V (AB) collagen as substrates. Human skin collagenase degraded types I, II, and III collagen, producing the characteristic 3/4 and 1/4 cleavage products, but failed to degrade type IV or V collagen. Collagenase prepared from the invasive tumors showed maximal activity after trypsin treatment. The tumor enzyme degraded type IV (basement membrane) collagen, producing fragments consistent with a single cleavage site but did not attack types I, II, III, and V collagen. Because type IV collagen prepared by pepsinization of placenta was also digested, it is likely that cleavage of type IV collagen by the tumor collagenase occurs within a largely helical domain. A type IV collagenase could play a significant role in tumor metastases and in normal tissues where basement membrane turnover takes place.
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PMID:Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. 22 20

Fibroblast cultures derived from human basal cell carcinomas demonstrated an increased capacity to synthesize and secrete collagenase. Although the levels of collagenase were up to 8-fold greater than those of normal control cell lines, this phenotypic trait was not permanent and was expressed only for a few passages following primary explanation. The basal cell carcinoma fibroblast collagenase was secreted as a proenzyme. The kinetics of activation and the catalytic efficiency of the basal cell carcinoma fibroblast enzyme were equal to control collagenase, indicating that increased activity was due to increased synthesis of enzyme protein. Increased synthesis of collagenase was not due either to altered cell growth or to an overall increase in protein synthesis. Furthermore, synthesis of another major protein, of another major protein, collagen, was not enhanced. The data suggest that the tumors may have stimulated adjacent fibroblasts to produce more collagenase which is of importance in tumor invasion.
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PMID:Enhanced collagenase production by fibroblasts derived from human basal cell carcinomas. 22 89

Histophysiology, ultrastructure, chemical analyses of transplants and implants of Dunn and Ridgway mouse osteosarcomas demonstrate that tumorigenesis is a manifestation of deranged morphogenesis in developing mesenchymal cell populations. The end product of development is defective, incompletely calcified, disorganized bone without any inclusions of bone marrow tissue. When Dunn osteosarcoma is freeze-dried and then implanted, the tumor is resorbed and replaced by deposits of normal cartilage, bone, and bone marrow. Freeze-dried Ridgway osteosarcoma is replaced only by a fibrous connective tissue scar. Disaggregated Dunn tumor osteoblasts synthesize a trypsin-labile collagenase-resistant cell surface localized bone morphogen. Tumor matrix stroma, prepared by sequential chemical extraction of soluble non-collagenous proteins also contains significant quantities of the same bone morphogen. Tumor tissue pulverized to particle size as small as 44 micrometer3 transmitted bone morphogen more rapidly than intact tumor tissue. The total tumor cell and stroma mediated bone morphogen produces three times more normal bone than normal cortical bone matrix. Our working hypothesis is that a normal bone morphogenetic polypeptide (BMP) is synthesized by Dunn osteosarcoma cells and retained by the tumor matrix stroma. Neither the mechanism of transmission nor the mesenchymal cell receptor sites of BMP are known.
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PMID:An osteosarcoma cell and matrix retained morphogen for normal bone formation. 27 29

When cultured in-vitro, originating from different breast cancer patients, tumor cells, identified histologically as carcinoma cells, varied in their proliferation patterns and cell morphology. If exposed for brief periods to vibrio cholera neuraminidaes (VCN), the amount of sialic acid released from the cells varied from one culture to another and increased with higher enzyme concentrations. If exposed to trypsin, the amount of released proteins varied also from one culture to another. Significant difference was observed between the effect of VCN or collagenase on normal and neoplastic cell cultures. Whether human or murine cell cultures, the cell-free media harvested from cultures of neoplastic cells containing high concentrations of collagenolytic-caseinolytic-fibrinolytic and esterolytic activities. Two effects of concanavalin A (Con A) have been distinguished on thymidine incorporation, the first is a decrease in the maximal thymidine uptake, whereas the second is a shift to the maximum thymidine uptake to higher Con A concentrations. At low concentrations, alpha-1-antitrypsin (AAT) had no effect, but at high concentrations it inhibited 3H-thymidine uptake. At low concentrations human profibrinolysin inhibited and at higher concentration sit enhanced uptake of the labeled precursor. Therefore, the collagen olytic caseinolytic-fibrinolytic enzyme is a pacemaker for proliferation of human mammary carcinoma cells.
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PMID:Human mammary carcinoma cells. The enzyme pacemaker profibrinolysin. 31 26

A method has been developed for studying in vitro the cell proliferation kinetics of human breast cancer, Surgical specimens from primary tumors were studied in 56 patients. Viable cell suspensions for assay were obtained by the dissociation of tumor tissue with collagenase. Mean Labeling indices of 2.43 +/- S.D 2.05 and 4.48 +/- S.D. 3.73, respectiviely, were found after incubation with 3HTdR for 2 hours and 24 hours. Mean S-times of 21.9 +/- S.D. 4.3 hours were estimated by 3H and 14C-TdR double-labeling. The kinetic data have been validated by parallel labeling studies in vivo and in vitro in four patients. The processing of autoradiographs using gold latensification provided slides for kinetic analysis within 3 days. The assay offers a method that is useful in the planning and monitoring of drug therapy.
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PMID:A rapid in vitro method for measuring cell proliferation in human breast cancer. 33 86


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