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)

Significant numbers of mast cells have been demonstrated histologically around the periphery of the invasive rat mammary adenocarcinoma 13672NF. The number of mast cells at microfoci along the tumour:host tissue junction was significantly greater than that found in normal mammary tissues, and few mast cells were detected within the tumour itself. Mast cell degranulation, often associated with disruption and lysis of the connective tissue matrix, was a common feature in later stages of tumour proliferation. When soluble products derived from purified rat peritoneal mast cells were added to monolayer cultures of rat stromal fibroblasts or tumour cells they stimulated a significant increase in total collagenase production, and the mast cell products were also capable of activating the latent collagenases thus produced. Histological examination indicated that degradation of local collagenous matrix was a common feature of mast cell degranulation, an observation possibly explained by the release of mast cell enzymes and/or the potential of this cell to modulate the expression of collagenolytic activity by surrounding cells. These observations suggest that, at least in some tumours, mast cells contribute to the connective tissue breakdown commonly associated with tumour invasiveness and metastatic spread.
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PMID:Mast cells and matrix degradation at sites of tumour invasion in rat mammary adenocarcinoma. 301 77

We have shown previously that an increase in tumor invasion and metastases occurred concurrently with a decrease in collagen content of the extracellular matrix surrounding the C3H mouse mammary adenocarcinoma borne by C3H/HeJ mice. In this paper we report the production of collagenase and elastase activities by the primary tumor cultures and three types of cloned C3H mouse mammary adenocarcinoma cell cultures. The primary tumor cell cultures and tumor-associated stromal cultures produced large amounts of collagenase and elastase activities. On the other hand, the primary tumor capsule cultures produced little or no collagenase and elastase activities even though they produced type I collagen. The production of proteases by the primary tumor cultures decreased along with time and with an alteration in the morphology of cell populations and/or passage of the cultures. The three clones of tumor cell cultures produced variable amounts of collagenase in response to induction by phorbol myristate acetate, an agent that stimulates maximal collagenase production. In contrast, all three cloned cultures elaborated significant amounts of elastase that degraded insoluble ligamental elastin, and most of the elastase production was increased further in response to induction by phorbol myristate acetate. Each cloned cell population exhibited differences in their production of collagenase and elastase in parallel with their difference in growth kinetics, yet these cells still possess the distinctive properties of the tumor. However, a unit amount of collagenase produced by each of the cloned cultures, with or without induction by phorbol myristate acetate, was less than that of the primary tumor cultures. Results suggest that some cell types or combination of cell types in the heterogeneous cell population of the tumor and/or their products appear to be responsible for the increased production of collagenase and elastase activities and for the invasiveness of a malignant tumor.
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PMID:Collagenase and elastase production by mouse mammary adenocarcinoma primary cultures and cloned cells. 302 19

It was previously shown that the administration of dexamethasone (Dex) to mice bearing mammary adenocarcinoma caused the collagen content of the tumor capsule to be decreased by 50%, but collagenase and other neutral protease activities of the tumor were the same as in the controls. These events occurred with distinctly increased tumor invasion and metastasis. The present communication reports on the characterization of capsule collagen and the effects of agents [vitamin A (VA) and Dex] on capsule collagen metabolism and presents further evidence concerning the possible mechanisms by which the collagen content of the capsule was decreased in the Dex-treated hosts. The collagen extracted from capsules of untreated controls and mice (C3H/HeJ) treated with VA or Dex was primarily type I, as judged by the migration of protein bands in sodium dodecylsulfate-polyacrylamide gel electrophoresis and by patterns of elution peaks from an octadecyl C-18 column. The amino acid compositions of type I collagen of the capsule of treated and untreated controls were similar but not identical to those of mouse skin and guinea pig skin type I collagens. The specific activity of intracellular free [14C] proline, the extent of hydroxylation of [14C]proline residues of collagen, and the specific activity of [14C]hydroxyproline and proline in each case were similar in treated and in untreated controls. These results suggest that the observed 45% decrease in the conversion of [14C]proline into protein-bound [14C]hydroxyproline of the Dex-treated hosts apparently was due to decreased collagen synthesis. The data also suggest that the most critical effects of Dex on tumor invasion and metastasis appeared to occur at an early stage before full formation of the collagenous extracellular matrix.
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PMID:Effects of vitamin A and dexamethasone on capsule collagen metabolism in mouse mammary adenocarcinoma. 302 97

The human colon adenocarcinoma cell line WiDr was xenografted and the tumor characterized. When athymic mice (NCR-nu) were inoculated with 10(6) cells, tumors appeared after 7-14 days with a 93-100% take rate and grew with an initial volume-doubling time of around 6 days. For optimizing the tumor disaggregation method, a comparison was made of two dissociation procedures and of different dissociation times. An enzyme cocktail (collagenase, DNase, pronase) resulted in total viable cell yields of 1-3 X 10(7) cells/g tumor tissue. Cell yield decreased with increasing tumor weight. Disaggregation with trypsin gave lower cell yields; and so, although the plating efficiencies (PEs) were higher, the enzyme cocktail was chosen for tumor disaggregation. On the basis of morphologic identification, cell suspensions prepared from WiDr tumors, by use of the enzyme cocktail for 2 hours, contained 49% malignant cells as well as a significant fraction of nonneoplastic cells. The major nonneoplastic host cell component was macrophage (33%); lymphocytes (13%) and granulocytes (5%) also were present. Host cells could be separated from neoplastic cells by centrifugal elutriation. By mixing various proportions of host and tumor cells, it was subsequently shown that the presence of host cells did not influence the malignant cell PE unless the cell suspensions contained greater than 90% host cells. Single-cell suspensions prepared from WiDr tumors, with use of the enzyme cocktail for 2 hours, were irradiated and then plated for survival (D0 = 1.5 Gy; n = 5) (D0, the 37% dose slope). A comparison was made of the sensitivity to radiation, after the different dissociation methods. The radiation sensitivities after 1.5-hour trypsinization and 2- and 6-hour enzyme cocktail administrations were similar, but after 0.5 hour of trypsin, the cells were more sensitive to radiation.
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PMID:A human colon adenocarcinoma xenograft--radiation response, cellular composition, and tumor disaggregation. 346 98

The experimental modulation of tight junctions (TJ) was studied in the human adenocarcinoma cell line HT 29 by freeze-fracture electron microscopy. The cell line has virtually no TJ when grown in culture. TJ could be induced by mild treatment with a variety of endopeptidases (trypsin, chymotrypsin, collagenase, elastase, plasmin, thrombin, papain, and pronase). Pronase induced the formation of TJ at low (but not at high) concentrations. All exopeptidases studied were unable to induce the formation of TJ. At 0 degree C the trypsin-induced formation of TJ was greatly slowed down although not entirely inhibited. However, when cells were briefly treated with trypsin at 0 degree C and subsequently transferred to 37 degrees C in the presence of protease inhibitors, TJ were rapidly assembled. Thus an induction phase at low temperature and an assembly phase at high temperature could be experimentally separated. When cells were briefly trypsinized at 0 degrees and subsequently kept at 0 degree C without trypsin for several hours, TJ still formed abundantly upon incubation at 37 degrees C. It appears therefore that the effect produced by the protease is retained for long periods in the cold.
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PMID:Formation of tight junctions in epithelial cells. I. Induction by proteases in a human colon carcinoma cell line. 388 Jul 1

Two clonal tumor subpopulations (designated as A and D) obtained originally from a heterogeneous human colon adenocarcinoma (DLD-1) were used to produce xenograft solid tumors in nude mice. First, disaggregation studies were performed to determine the optimal choice of enzyme and time of dissociation for the pure A and D neoplasms, using cell yield (cells/mg/min) and colony forming efficiency (CFE) assays. The enzymes investigated were: 0.5 or 0.2% trypsin, and two cocktails containing pronase (0.5 or 0.05%), collagenase (0.02%), and DNAse I (0.02%). For the 0.5% trypsin treatments, the cell yield from A and D tumor fragments increased until about 30 min, at which time a plateau in cell yield was reached. A plateau in CFE was also reached at this time. In contrast, the cell yields for the 0.2% trypsin treatment did not reach a plateau within the time of the dissociation (120 min), and the CFEs were lower than with the 0.5% trypsin. Whereas no differences in cell yield or CFE were found between the enzyme cocktail studies (0.5% trypsin vs. 0.05% pronase), the cell yield and the CFE from the clone D carcinomas were significantly less than that found with the 0.5% trypsin (the cell yield and CFE from clone A tumors were identical for 0.5% trypsin or enzyme cocktail). These data indicate that, while these clonal neoplasms have somewhat different responses to enzyme disaggregation, it is possible to select an enzyme treatment and treatment time that is appropriate for use on both A and D tumors (i.e., 0.5% trypsin). After determination of an acceptable enzyme procedure, 'reconstructed' heterogeneous tumors produced from an initial injection bolus of 50% clone A and 50% clone D cells were disaggregated as a function of time (days 12-83 postinjection). Over this period, we found that the cell yield decreased exponentially, with a half-time (T1/2) of 20.5 +/- 7.3 days (95% confidence limits), with a maximum extrapolated cell yield at time zero of about 1.2 X 10(5) cells/mg. The CFE was essentially constant over the duration of the assay period. Moreover, it was found that the percentage of clone A cells appeared to decrease exponentially (T1/2 = 20.5 +/- 11.5 days, 95% confidence limits) until about 40 days postinjection. After this time an equilibrium mixture consisting of about 10% clone A cells and 90% clone D cells was reached.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Disaggregation studies of xenograft solid tumors grown from pure or admixed clonal subpopulations from a heterogeneous human colon adenocarcinoma. 406 5

Both malignant (adenocarcinomas) and nonmalignant (fibroadenomas and normal tissue) human breast tissues were maintained in organ culture for up to 10 days to study the secretion of lysosomal and neutral proteinases. Little difference was observed between the different tissue groups in the release of the lysosomal proteinase cathepsin D into the culture medium. Similar results were obtained when media were tested for plasminogen activator activity. The secretion of collagenolytic activity was investigated with fibroadenoma and adenocarcinoma explants and found to be very low for both tissue groups. The average accumulation of collagenase activity during a 2-day period was 0.002 units/microgram DNA for adenocarcinomas and 0.008 units/microgram DNA for fibroadenomas. The only proteinase that was secreted in substantially higher amounts from explants of malignant tissue was a cathepsin B-like thiol proteinase. Media from adenocarcinoma explants (n = 38) contained on the average 11 times more activity than did media from fibroadenoma (n = 20) and normal tissue explants (n = 8). Metastases of mammary adenocarcinomas (n = 7) secreted the thiol proteinase at about one third of the rate of primary tumors. The secretion of this enzyme is dependent upon protein synthesis as its release was completely inhibited 24 hr after the addition of cycloheximide. In some cases, it was also observed that the presence of sheep serum in the tissue culture medium reduced the accumulation of activity.
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PMID:Secretion of proteinases from malignant and nonmalignant human breast tissue. 625 82

A spontaneous mammary adenocarcinoma (AC) from an inbred female rat was investigated with regard to secretion of neutral proteases. Cultures of neoplastic epithelial cells derived from the tumour secreted an enzyme that fulfilled the criteria for a specific collagenase. In contrast to cultures of non-neoplastic cells, tumour collagenase was present as an active enzyme, since treatment with trypsin or p-aminophenylmercuric acetate (APMA) did not increase activity. The neoplastic cells were also prolific producers of plasminogen activator (PA). Dexamethasone (Dex) (10(-6)M) markedly reduced the levels of both enzymes. Addition of tranexamic acid (TA), an inhibitor of plasmin and of plasminogen activation, did not affect collagenase activity, even at 10(-1)M TA, nor did latent collagenase accumulate. Latent collagenase was secreted in culture by normal fibroblasts from neonatal rat lungs. This latent enzyme was activated by the addition of tumour cell medium plus plasminogen, but this effect was inhibited by the addition of TA. These results demonstrate that the neoplastic cells themselves secrete collagenase as an active enzyme. PA is also secreted, is not involved with tumour collagenase, but is capable, in the presence of plasminogen, of activating latent collagenase produced by the non-neoplastic cells within the tumour or in the surrounding tissue. This tumour possesses potent collagenolytic ability in vitro which may be partly responsible for its rapid invasion in vivo.
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PMID:Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator. 627 36

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

The process of metastasis involves numerous steps, many of which are thought to require the action of hydrolases, such as collagenase and other proteases. In this study, we investigate the role of the protease plasminogen activator in the metastasis of the rat mammary adenocarcinoma 13762. We observed that this tumor cell line is heterogeneous with respect to plasminogen activator (PAA) production. Clonal tumor cell populations were isolated which produced various levels of PAA. This phenotypic property of these clones remained stable for long periods of in vitro culture and did not affect their tumorigenicity. When the metastatic potential of these clones was determined using the lung colony assay, a strong correlation between PAA and metastatic potential was found. Furthermore, a threshold level of PAA production was observed, above which the lung colony-forming ability of the cells increased dramatically. These studies suggest that PAA production may play an important role in tumor metastasis.
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PMID:Involvement of plasminogen activator production with tumor metastasis in a rat model. 653 67


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