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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cysteine had been reported to increase survival time in thymoma-bearing mice and the interpretation suggested was that this was due to inhibition of a collagenase activity associated with some tumor cells by a chelating action of cysteine. In the present work it was shown that cysteine was a particularly potent inhibitor of amino acid transport into S37 ascites tumor cells, raising another possible interpretation of the earlier data. Sarcomas have previously been reported to lack collagenase activity; a survival study using S37 cells was therefore undertaken in an attempt to distinguish between possible interpretations of the earlier data involving thymomas. A null result was obtained with either cysteine or EDTA, reinforcing the earlier interpretation that survival enhancement with thymoma-bearing mice was due to an effect on collagenase. Other sulfhydryl analogs were found to inhibit transport also, and the effect was more pronounced with system L than system A. The reason for cysteine's particularly potent action on amino acid transport may be associated either with chelation of a metal ion involved in transport, or the involvement of the gamma-glutamyl cycle in the support of amino acid transport.
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PMID:Effects of cysteine upon tumor cells. 2 29

A specific collagenase (EC 3.4.24.3) has been found and purified from serum-free culture medium of 11095 epidermoid carcinoma of rat prostate. The molecular weight of this collagenase was estimated at 71 000 and the pH optimum was approx. 7. At 26 degrees C, the collagenase cleaved collagen at a site 3/4 the length from the N-terminus. At 37 degrees C, this collagenase degraded collagen to smaller peptides. The enzyme activity was inhibited by serum, cysteine and EDTA, but not by protease inhibitors. The presence of collagenase in rat tumor tissue suggests that this enzyme might play a significant role in tissue invasion by cancer cells.
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PMID:Collagenase activity in cultures of rat prostate carcinoma. 3 9

Proteases capable of activating procollagenase from gingiva and from fibroblast and macrophage monolayer cultures were harvested from homogenates of canine tumor mast cells. The mast cell proteases lysed casein and Azocoll but not native collagen. In low salt concentrations the enzymes existed at high molecular weight complexes, which were dissociated by increasing the salt concentration above 1.0 M (NaCl, KCl). Gel filtration in 1.4 M KCl separated the protease activity into three peaks, all of which activated procollagenase. Two of the enzymes showed substrate specificities (hydrolysis of p-tosyl-L-arginine methyl ester and benzoyl-tyrosine ethyl ester) and reactive center reactivities similar to pancreatic trypsin and chymotrypsin. Based on gel filtration, apparent molecular weights of 160 000 (p-tosyl-L-arginine methyl ester esterase), 90 000 (main procollagenase activator) and 36 000 benzoyl-tyrosine ethyl ester esterase) were determined. Activation of procollagenase resulted in a 18-20 000 decrease of the molecular weight. The activation was directly related to the amount of activator added within certain limits. Further addition of activator resulted in proteolytic inactivation of collagenase.
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PMID:Activation of fibroblast procollagenase by mast cell proteases. 5 9

Urogenital tissue specimens were maintained in culture for 2 years. Epithelioid growth was enhanced with use of collagenase digestion rather than trypsinization. Twenty of 34 prostate cancer cell cultures survived more than ten in vitro passages, during which time four of 20 demonstrated epithelioid morphology. One epithelioid line (T-157) survived 32 in vitro passages. The cells demonstrated lack of contact inhibition in culture, were slightly positive in acid phosphatase tests, and reacted positively with cytomegalovirus (CMV)-immune sera in indirect immunofluorescence (IF) tests. These cells, which were proven to be of human male origin, failed to yield infectious virus and could be re-isolated from a nodule induced by the cells when injected sc into weanling athymic nude mice. The serum of the patient from which the tumor cells were derived demonstrated high CMV antibody titers and reacted with the virus-specific membrane and intracellular antigens of CMV-transformed human cells in IF tests. A CMV strain isolated from one of the normal prostate cell cultures established an in vitro long-term persistent infection of human embryo lung cells which resulted in the development of two transformed cell lines. The transformed cells possessed CMV antigenic markers and induced non-differentiated tumors when transplanted into athymic nude mice. The results constitute further evidence of the transforming capacity of CMV, and suggest that the virus may be oncogenic in its natural (human) host.
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PMID:Cytomegalovirus and cancer of the prostate: in vitro transformation of human cells. 6 20

Giant cell tumors of bone obtained from 7 patients were dispersed with clostridial collagenase and trypsin and adherent cells were maintained in culture. Early cultures contained both mononucleated and multinucleated cells presumably derived from the stromal and giant cells of the original tumor. The original multinucleated cells did not survive for greater than 7-10 days whereas the mononucleated cells persisted and could be passaged by trypsinization. In 5 of 7 early cultures exposed to parathyroid hormone (PTH) there was a rise in cAMP within 5-10 min in both cells and medium which averaged approximately 12-fold. None of the cells responded to calcitonin and a variable rise in cAMP was seen after incubation with prostaglandin E2. In cells cultured from 3 tumors the PTH response disappeared with passage of the cells, but in the remaining 2, PTH response persisted through multiple passages. The presence as well as the magnitude of the PTH-induced cAMP response in these cells is consistent with a skeletal origin.
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PMID:Response to hormones of cells cultured from human giant cell tumors of bone. 8

Cells derived from human atherosclerotic plaques and from arterial media were compared with cells obtained from human leiomyomata and myometrium with respect to growth behavior in long-term cell culture. None of numerous variations in culture media, including alterations of serum concentration and source, improved the rate of cell multiplication or in vitro longevity. Both uterine cell types, but neither arterial cell type, multiplied after tissue dissociation with enzymes (elastase, collagenase, hyaluronidase). The replicative life-span of each of eight samples of arterial plaque cells was equal to or less than that of the corresponding medial cells. A similar relationship was observed for eight paired sets of leiomyoma and myometrial cells. The results indicate that, under the conditions of culture in vitro, cells of a bona fide smooth muscle tumor have a finite replicative life-span and smooth muscle cells of atherosclerotic plaques behave in a similar manner.
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PMID:Human atherosclerotic plaque cells and leiomyoma cells. Comparison of in vitro growth characteristics. 16 92

Summary--Tumor invasion requires the breadkdown of the main structural protein, collagen. A series of fourteen epidermoid carcinomas of the larynx and oral cavity produced a collagen dissolving enzyme in vitro as demonstrated by the breakdown of 14C-labeled collagen. Oral cavity tumors showed greater activity than laryngeal carcinomas while both sites were more active than uninvolved mucosa from the same patients. Tumor associated collagenase activity, in common with previously described collagenases, can only be demonstrated in vitro and requires protein synthesis. Maximum tumor collagenase occurred at 24 hours in vitro and then declined as compared with the maximum collagenase at 72 hours in vitro produced by oral cavity mucosa. The 14 patients in our series were ranked in order of the collagenase activity of their tumors. At 18 months after the diagnosis, four of the six patients with the most active tumors were dead of cancer and one patient was alive with persistent cancer. High collagenase activity may be a factor in the clinical aggressiveness of epidermoid carcinomas of the head and neck.
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PMID:Collagenase activity in epidermoid carcinoma of the oral cavity and larynx. 16 14

An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of "soft" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, "scirrhous" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.
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PMID:Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer. 16 44

Collagenase cleavage of human Type II and III collagens has been studied using a highly purified preparation of rabbit tumor collagenase. Progress of the reactions in solution was followed by viscometry and the results indicated that under the conditions employed Type III collagen molecules were cleaved at approximately five times the rate of Type II molecules. Cleavage products of the reactions were isolated in denatured form by agarose molecular sieve chromatography. The molecular weights and amino acid compositions of the products demonstrated that Type II and III molecules had been cleaved at the characteristic three-quarter, one-quarter locus, giving rise to a large fragment derived from the NH2-terminal portion of the molecule and a smaller fragment representing the COOH-terminal region. The amino acid sequence at the NH2-terminal portion of the smaller fragment derived from Type II collagen was determined to be Ile-Ala-Gly-Gln-Arg, and the corresponding region from Type III collagen was found to have the sequence Leu-Ala Gly-Leu-Arg. These sequences for alpha1(II) and alpha1(III) chains adjacent to the site of collagenase cleavage along with previous data for alpha1(I) and alpha2 chains indicate that the minimum specific sequence required for collagenase cleavage is Gly-Ile-Ala or Gly-Leu-Ala. Inspection of the available sequence data for collagen alpha chains indicates that the latter sequences are found in at least three additional locations at which collagenase cleavage does not occur. Each of the sequences which are apparently not substrates for collagenase, however, are followed by a Gly-X-Hyp sequence. We suggest, then, that a minimum of five residues in collagen alpha chains COOH-terminal to the cleavage site comprise the substrate recognition site.
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PMID:Cleavage of Type II and III collagens with mammalian collagenase: site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens. 17 19

A human pancreatic beta cell tumor was maintained in monolayer cell culture for 80 days. The culture was terminated because of bacterial infection. Probably because extensive trypsin-collagenase dissociation was unnecessary, the dissociated cells attached much more quickly to the surface of the culture flask than do rat pancreatic cells obtained by enzymatic dissociation. Insulin release not only oscillated widely during the first 40 days of culture but also showed a decline from 380 mU the first week to about 50 mU/week the seventh week. For some unknown reason fibroblast overgrowth was not a major problem. Reduction of the medium glucose concentration from 16.5 mM to 5.5 mM did not alter insulin release rate. At glucose concentration of 16.5 mM, somatostatin 1.0 mug/ml reduced insulin release by 40%. From our previously reported studies on the effect of somatostatin on insulin release by monolayer cell cultures of rat endocrine pancreas, we conclude that the constant release of insulin by the tumor cells is relatively nonstimulated. We have confirmed that monolayer cultures of human pancreatic beta cell tumor do not represent a good model for normal human beta cell function because of the major shortcoming of an apparent inability to recognize glucose as a secretogogue.
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PMID:Monolayer cell culture of human pancreatic beta cell tumor: effect of glucose and somatostatin on insulin release. 17 3


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