Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighteen clones of a methylcholanthrene-induced murine fibrosarcoma (3AM) which were heterogeneous with respect to metastatic potentials and in vivo growth rates were examined for five different protease activities: acid protease (cathepsin D), BANA hydrolase (cathepsin B), neutral protease, collagenase, and plasminogen activator. Homogenates of the solid tumors produced by the clones were heterogeneous with respect to the activities of the proteases; these activities were in all cases (except plasminogen activator) higher than those obtained for normal muscle tissue. There was, however, no correlation between any of these protease activities and the metastatic potential or in vivo growth rates. The cathepsin B activity has also been evaluated on the cultured cells of the various clones. Results similar to that of the in vivo study were obtained. Analysis of the enzyme activity of the cell culture and of organ culture media, however, revealed no cathepsin B activity. It is concluded that the measurement of any one biochemical parameter such as proteolysis may not be sufficient to establish a correlation with the overall process of metastasis; a more precise dissection of the individual steps culminating in metastasis may provide a more fruitful approach to this problem.
Clin Exp Metastasis
PMID:Proteolytic and metastatic activities of clones derived from a methylcholanthrene-induced murine fibrosarcoma. 610 Aug 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

Much of the effort of this laboratory in recent years has been directed towards developing a reliable protocol for the experimental analysis of factors affecting metastatic spread from naturally occurring (i.e. not transplanted) neoplasms. The objective of this has been to develop a data base on the variations in metastatic behaviour between spontaneously arising neoplasms and to examine the tumour-specific and host-specific mechanisms accounting for this. This paper details the experimental technique and underlying conceptual basis which have been developed for reproducible investigations of this subject. It also reviews our conclusions from such work on the role in metastatic spread of tumour cell surface properties, collagenase secretion, microenvironmental effects on tumour cell growth in various organs, tumour macrophage content, and degree of cell shedding into the bloodstream.
Cancer Metastasis Rev 1982
PMID:Investigations of the mechanisms of metastatic spread of naturally occurring neoplasms. 630 67

Collagenases are a family of metalloproteinases which may play a role in facilitating tumor cell invasion of the extracellular matrix. Tumor cells traverse two types of extracellular matrix: basement membranes and interstitial stroma, at multiple stages of the metastatic process. The matrix is a dense meshwork of collagen, proteoglycans, elastin and glycoproteins. Normally the matrix does not contain open spaces large enough for cell movement. Therefore numerous investigators have postulated that collagenolytic proteases, secreted by tumor cells or associated host cells, breakdown the extracellular matrix during tumor cell invasion. A large number of animal and human tumors have been shown to contain collagenase at a higher level than corresponding benign tissues. Separate collagenolytic metalloproteinases have been identified which degrade specific types of collagen. A basement membrane collagenolytic protease was shown to be elevated in a series of metastatic murine tumor cells. Immunologic studies using antibodies specific for collagenase have demonstrated that in vivo, tumor cells can produce collagenase. Therefore identification of collagenase in cultured lines of tumor cells is not an artifact of in vitro cultivation. In some cases, tumor cells may induce host cells to produce collagenase. The best evidence to date that collagenases actually play a role in invasion is derived from experiments in which natural collagenase inhibitors block tumor cell invasion of extracellular matrix in vitro.
Cancer Metastasis Rev 1982
PMID:Role of collagenases in tumor cell invasion. 630 68

The production of collagenase and collagenase inhibitor (TIMP) by various intracranial tumors (25 meningiomas, eight gliomas, seven metastases, four pituitary adenomas, and five others) was studied in short-term organ culture. While meningiomas produced negligible amounts of collagenase, two metastatic carcinomas of bronchial and breast origin produced significant amounts of the enzyme. Cultures of dura from an invasive meningioma and of bone invaded by a meningioma also produced collagenase. In varying amounts, TIMP was detected in culture media from most of the tumors studied; invasive tumors tended to produce less TIMP than noninvasive tumors. The results are discussed in relation to current views on tissue degradation and mechanisms of tumor invasion.
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PMID:Production of collagenase and inhibitor (TIMP) by intracranial tumors and dura in vitro. 631 67

Proteolytic and sialyltransferase activities were determined in extracts of 65 human primary breast tumors, 6 lymph node metastases, 6 fibroadenomas and 27 normal tissues. Using proteins and synthetic selective substrates, we observed the presence of collagen-peptidases, plasminogen activator, cathepsin-B and cathepsin-D-like enzymes, and sialyltransferase. No active or trypsin-activatable type-IV collagenase activity was detected. Although individual variations between tumors were large, proteinase and sialyltransferase contents were significantly elevated in malignant breast tissues. Enzyme activities were found to be related to the epithelial volume of the tumor. No significant correlation was found between the proteinase or sialyltransferase activities and the degree of differentiation of the tumor cells, or the degree to which tumors had metastasized to regional lymph nodes. Since large variations of enzyme levels apparently reflect the heterogeneity of epithelial cell densities in tumor samples, proteolytic or sialyltransferase activities cannot therefore be used as a measure of quantitative evaluation of invasive properties in breast cancer.
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PMID:Proteinases and sialyltransferase in human breast tumors. 632 71

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.
Invasion Metastasis 1984
PMID:Extracellular cysteine proteinase and collagenase activities as a consequence of tumor-host interaction in the rabbit V2 carcinoma. 632 87

Naturally occurring renal adenocarcinoma in North American leopard frogs, Rana pipiens, metastasize frequently (77%) when these ectothermic animals are kept in a warm environment but not when they are kept cold. We have found that explants of these tumors secrete collagenase, an enzyme capable of dissolving connective tissue fibers and found previously to be closely correlated with metastatic colony-forming capability of murine mammary tumors, and that the amount released sequentially rises and falls as the ambient temperature is shifted between metastasis-permissive and -inhibitory levels. In contrast, normal frog renal tissue has low collagenase output, unaffected by temperature changes.
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PMID:Temperature-dependent elaboration of collagenase by the renal adenocarcinoma of the leopard frog, Rana pipiens. 633 46

MCF-7 cells, a human breast carcinoma line, forms tumors when injected into athymic nude mice. These tumors are able to metastasize to lungs, liver and spleen. 17 beta-estradiol treatment increases both the growth rate and frequency of metastases. Castration or diabetes prevents metastasis formation, but treatment with estrogen or insulin restores the metastasizing capacity. MCF-7 cells secrete into the culture media collagenases able to lyse types I and IV collagens. Estrogen or insulin addition to the culture enhances collagenase production. Attention is called to the coexistence of enhancement in collagenase production and metastasis formation.
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PMID:Formation of metastasis by human breast carcinoma cells (MCF-7) in nude mice. 645 Jun 36

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


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