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)

For the investigation of the pathogenesis of desmoplasia, the capacities to synthesize collagen in vitro of 2 bile duct carcinomas (lines 1 and 10) of Sewall-Wright inbred strain 2 guinea pigs and of syngeneic dermal fibroblasts were studied. Line 10 cells synthesized collagen type IV as judged by sensitivity to bacterial collagenase, by immunoprecipitation, by migration of pro alpha (IV) chains and pepsin-resistant fragments on sodium dodecyl sulfate-polyacrylamide gels, and by immunofluorescence. Line 1 cells also synthesized small amounts of collagenase-sensitive protein. Neither line 1 nor line 10 cells synthesized detectable collagen type I, III, or V. Only about 1% of [14C]proline incorporated by tumor cells was found in collagenase-sensitive protein. In contrast, dermal fibroblasts synthesized 4 and 128 times as much collagenase-sensitive protein as line 10 and line 1 cells, respectively, amounting to 20% of total protein synthesized. Fibroblasts produced mostly collagen types I and III, in a ratio of 7:1, and smaller amounts of collagen type V. Thus lines 1 and 10 carcinoma cells produce primarily basement membrane collagen, whereas interstitial collagens, abundant in desmoplastic tumor stroma, are fibroblast products.
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PMID:Pathogenesis of tumor desmoplasia. II. Collagens synthesized by line 1 and line 10 guinea pig carcinoma cells and by syngeneic fibroblasts in vitro. 609 69

Mouse monoclonal antibodies to various human epidermal and basement membrane components were formed by immunizing Balb/c mice with ME-180, a line of human cervical carcinoma cells. The spleen cells from hyperimmunized mice were fused with a nonsecreting mouse myeloma cell line using polyethylene glycol. The resulting hybrids were selected by growth in media containing 20% fetal calf serum, hypoxanthine, thymidine, and methotrexate in RPMI-1640 in 24-well Linbro plates. Wells producing antibodies of interest were grown and eventually cloned over an HGPRT- rat fibroblast feeder layer. These cultures were expanded and recloned. Two cloned antibodies of interest are DUX 5.2 and DUX 1.1.3. DUX 5.2 is the mouse IgG1 subclass and reacts with the membranes of ME-180 cells and the human skin epidermal basement membrane zone as shown by direct immunofluorescent microscopy. Ultrastructural localization using electron microscopic immunoperoxidase techniques showed localization of the DUX 5.2 antigen to be beneath the lamina densa; the reaction product may include the anchoring fibrils. Although DUX 5.2 reacts with the normal human basement membrane zone and the basement membrane zone in several diseases, there is no reactivity in the normal, never-blistered skin of patients with dystrophic epidermolysis bullosa (DEB). This suggests that the increased collagenase in the disease may be destroying antigenicity of the antigen recognized by DUX 5.2 or that the antigen may not be present in DEB. This antibody will thus allow early neonatal and prenatal diagnosis in DEB and allow isolation of the structural moiety which is deficient in DEB. DUX 1.1 is an IgM mouse immunoglobulin specific for the cytoplasm of human basal cells. Its reactivity with upper epidermis is significantly less than that seen in the basal layer. All cells of the basal layer stain uniformly. The slight amount of staining in upper cells probably represents dilution of antigen which is not synthesized beyond the basal layer. Basal cells of hair follicles and sweat glands are stained to some degree.
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PMID:Monoclonal antibodies to normal and abnormal epithelial antigens. 619 49

Tumor invasion has been correlated with the ability of tumor cells to produce collagenolytic enzymes which are capable of degrading normal host tissues. However, the human small cell carcinoma implanted subcutanouesly and growing progressively in athymic (nude) mice produced large quantities of collagenase but did not appear to significantly infultrate adjacent host tissue. In comparison, subcutaneously implanted murine Lewis lung tumors produced similar quantities of collagenase and were locally invasive. The human tumors were surrounded by a compact layer of fibroblast cells in a fibrous matrix. This fibrous sheath exhibited anticollagenase activity and indicated a mechanism of host tissue resistance to invasion via the formation of inhibitors to degradative enzymes produced by tumor cells.
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PMID:Collagenase inhibitors retarding invasion of a human tumor in nude mice. 624 91

Medroxyprogesterone, dexamethasone, or cortisone, locally applied in sustained release polymer to rabbit V2 carcinoma implanted in the rabbit cornea, blocked neovascularization and three-dimensional growth of the tumor. These hormones similarly prevented the vascular proliferative response to implants in the rabbit cornea of mouse B-16 melanoma and also the response to implants of polymer containing tumor extract with angiogenesis activity. The inhibitory responses were accompanied by considerable reduction in collagenolytic activity released into culture medium by explants of the two tumors and of the corneal region containing angiogenic hepatoma extract. Morphologic studies revealed extensive three-dimensional disruption of the compact laminated collagenous structure of the cornea by untreated V2 carcinoma. In the presence of hormone the tumor grew slowly as a noninvasive two-dimensional plaque limited to the narrow region of the insertion pocket in the cornea, with no obvious disturbance of structure elsewhere. Cortisone was much les effective than medroxyprogesterone or dexamethasone. Testosterone and estradiol had no effect on the three measured properties. The data suggest that local hormonal interference with neovascularization, collagenase production, and tumor growth can prevent neoplastic invasion and destruction of a dense collagenous connective tissue.
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PMID:Inhibition of tumor growth, vascularization, and collagenolysis in the rabbit cornea by medroxyprogesterone. 626 56

Extracellular matrix proteins synthesized and secreted by adherent human tumor cell lines were analyzed using metabolic labelling with glycine and proline in the presence of ascorbate, polypeptide analysis and polyacrylamide gel electrophoresis, affinity chromatography, collagenase digestion, and immunofluorescence staining. The results showed a characteristic pattern of matrix proteins for each tumor cell type. Tumor cell lines of mesenchymal origin produced mostly interstitial types (I and II) of collagen and fibronectin. Carcinoma cell lines secreted only basement membrane proteins, type IV collagen, laminin and fibronectin, but not interstitial collagen. A melanoma and a rhabdomyosarcoma cell line produced type V of procollagen that has not previously been described in cell culture. Neuroblastoma cells were shown to be phenotypically heterogeneous also with respect to matrix protein production. We propose that the analysis of extracellular matrix proteins may serve as an adjunct in the classification of human tumors.
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PMID:Extracellular matrix proteins characterize human tumor cell lines. 627 24

The relative contribution of host cells and tumor cells to the production of collagenase and its regulation during tumorigenesis were studied with the use of a heterologous rabbit tumor-nude mouse host system. The V2 carcinoma, a malignant neoplasm of the New Zealand White rabbit, behaved as a nonmetastasizing, noninvasive tumor when implanted and grown in the inbred Swiss albino nude mouse. The extracts from both tumors contained similar levels of collagenase. Tumor explants also released enzyme into culture medium in both cases, but the rabbit tumor produced approximately 10 times more collagenase than the nude mouse. Freeze-thawing of the explants or treatment with cycloheximide markedly inhibited the appearance of enzyme in the medium from the rabbit tumor but not from the nude mouse tumor. The relative proportions of mouse- and rabbit-derived collagenase in the nude mouse tumor extracts and culture medium were determined with the use of antibodies specific for rabbit V2 tumor and mouse bone collagenases. Approximately 70% of the nude mouse tumor enzyme was derived from the rabbit tumor, and approximately 30% was derived from the mouse host. These findings indicate that the former might represent stored enzyme carried over during tumor transplantation into the nude mouse, whereas the latter might have originated from stimulation of host cells during tumorigenesis.
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PMID:Collagenolytic activity of rabbit V2 carcinoma implanted in the nude mouse. 629 64

Fibroblast-like cells (F-cells) and epithelial-like (E-cells) derived from cultures of rabbit VX-2 carcinoma released collagenase in both active and latent forms in serum-free medium at a level higher than that of normal rabbit fibroblast cultures. The enhanced capacity of the F-cells to release the enzyme, however, continued only for a few passages and then decreased significantly to a low level similar to that of the normal fibroblasts. The enzyme-release by the E-cells continued for a few more passages at a relatively moderate level, higher than that of normal fibroblasts. The release of collagenase in cultures of F-cells was enhanced by the presence of E-cells in mixed cultures as well as by medium conditioned by the E-cells type. Addition of cytochalasin B at 2 micrograms/ml did not significantly effect the enzyme activity released in the cultures. Serum from tumor-bearing rabbits appeared to stimulate the release of enzyme activity in cultures of either cell type.
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PMID:Collagenase activity in rabbit carcinoma: cell source and cell interactions. 629 30

Primary and secondary cultures of VX-2 carcinoma produced high levels of collagenase activity in both active and latent forms in serum-free media. These cultures appeared morphologically heterogeneous in phase-contrast microscopy and revealed the presence of mainly three distinct forms: epithelial-like cells (E cells), fibroblast-like cells (F cells), and large rounded-flat cells which may represent a subclass of the F cells. Cell separation techniques such as brief dispase treatment, Percoll gradient centrifugation, thimerosal treatment, and rabbit serum were used to obtain predominantly one form or the other. The E cells never formed a monolayer but rather grew as limited size clusters of intimately associated cells with large nuclei and often appeared multinucleated. These cells were difficult to maintain in culture or serially passed more than a few times. The F cells, rare in early cultures but having the highest growth potential, appeared in various morphological forms ranging from spindle- to stellate-shaped cells. The cells in their third passage were capable of producing palpable tumors, similar in light and electron microscopic studies to the original tumor from which they were derived, when injected intramuscularly into recipient rabbits and produced specific collagenase activity in active and latent forms in serum-free media. Ultrastructural studies suggested that the E cells were of epithelial origin whereas the F cells were similar to stromal fibroblasts. Cytogenetic studies demonstrated that almost all of the E cells showed both numerical and structural chromosomal changes in a modal number of 54 chromosomes. On the other hand, the major cell population of the F cells resembled normal rabbit fibroblasts; both contained a normal diploid (2n = 44). However, few cells (4-6%) in the F-cell population were hyperdiploid with a modal chromosome number of 54. These cells may represent inadvertent contaminating E cells and account for the apparent limited turmorigenicity observed in early F-cell cultures. The data suggested that the E cells were of tumor origin whereas the majority of the F-cell population appeared to be of host origin. Furthermore, it is suggested that the E cells stimulate tumor-associated stromal cells to produce elevated levels of collagenolytic activity and contribute to collagen degradation during tumor invasion.
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PMID:Separation of VX-2 rabbit carcinoma-derived cells capable of releasing collagenase. 629 79

A new modification of the organ culture technique is described. In contrast to the conventional technique in which organ pieces (1 mm3) are cultivated, uniform, viable, microscopically controlled tissue slices are used in a modified organ culture technique. The new method is suitable for in vitro culture of human mammary carcinoma. Flow cytometry measurements reveal changes prior to and after collagenase treatment of human mammary carcinomas. In organ culture the composition of cell population prior to and after 48 h could be maintained. Examination under the microscope confirmed these results. The uptake of [3H]-thymidine was greater in tumor slices than in tumor pieces. Organ cultures sufficiently represent carcinoma in vivo in comparison to the other mentioned in vitro techniques.
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PMID:[In vitro cultivation of vital tissue slices: a new variation of organ culture technics]. 631 48

Specimens of the rabbit V2 carcinoma were maintained in organ culture to study the secretion of proteinases. Elastase-like, chymotrypsin-like, plasminogen activator-like, cathepsin B-like and collagenase activities were assayed with sensitive fluorimetric techniques. Of these enzymes, the only activities that were secreted in considerable amounts in primary cultures of tumor tissue were collagenase and a cysteine proteinase resembling cathepsin B. Co-cultures of intraperitoneally grown tumor and normal subcutaneous tissue of the rabbit resulted in significantly higher production of the cysteine proteinase and collagenase compared to the sum of the activities of the separate tissues. Explants of subcutaneous tissue of tumor-bearing rabbits secreted significantly more cysteine proteinase and collagenase than explants from normal animals. Explants from normal subcutaneous tissue stimulated with tumor-conditioned culture medium secreted both enzymes in higher amounts compared to the controls. The cysteine proteinase was similar in some properties to rabbit liver cathepsin B, but the enzyme from the tumor-host system showed a remarkable stability to a moderately alkaline pH. We suggest that a diffusible factor, derived from the tumor or immigrated cells, promotes an increased synthesis and secretion of collagenase and cysteine proteinase in the host, and that both enzymes may play cooperative roles during invasion of the surrounding tissues by the V2 carcinoma.
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PMID:Extracellular cysteine proteinase and collagenase activities as a consequence of tumor-host interaction in the rabbit V2 carcinoma. 632 87


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