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

Orthotopic implantation of human colon carcinoma cells is useful for studying the behavior of metastatic subpopulations. We observed that the parental line and variants of human colon carcinoma KM12 cells were all tumorigenic following implantation into the subcutis or cecal wall of BALB/c nude mice. Their ability to metastasize to distant organ sites varied, however, with the site of growth. Subcutaneous (SC) tumors did not produce visceral metastases, whereas cecal tumors metastasized to the regional mesenteric lymph nodes and to the liver. To examine the influence of organ environment on the extracellular matrix-degrading activity of the tumors, we inoculated human colon carcinoma cells into the subcutis or cecal wall and after 7 weeks isolated and cultured the tumors in serum-free medium. The conditioned media of SC tumors contained very low levels of type IV collagenase (gelatinase) and heparanase (heparan sulfate-specific endo-beta-D-glucuronidase), whereas the media of the cecal wall tumors contained high levels of both. Zymograms of the media revealed that the intracecal human colon carcinomas secreted more than three times the amount of latent and active forms of 92-kd type IV collagenase than did the SC tumors. Moreover, only the conditioned media of intracecal tumors contained latent and active forms of 64-kd type IV collagenase. Histochemical analysis using rabbit antiserum raised against the synthetic peptides of 72-kd procollagenase type IV showed type IV collagenase in the intracecal tumors; human colon carcinoma growing SC, however, were not stained significantly. These results suggest that factors in the organ environment may affect production and secretion of tumor extracellular matrix-degrading enzymes, and these factors may modify the metastatic behavior of human colon carcinoma cells in nude mice.
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PMID:Influence of organ environment on extracellular matrix degradative activity and metastasis of human colon carcinoma cells. 225 Mar 3

In order to investigate the role of collagenase in cancer invasion and metastasis, two collagenase activities of interstitial collagenase and type IV collagen degrading enzyme (type IV collagenase) were determined in 40 cases of human stomach cancer tissue. Elevated cancers which are known to have a propensity to cause blood-borne metastases showed higher activities of both interstitial collagenase and type IV collagenase than flat or ulcerous type of cancer. Using the parameters of lymph node metastasis vs tumor size or vs depth of cancerous invasion into the stomach wall, classification of the cases was attempted according to the degree of malignancy. In the cases with marked lymph node metastases in spite of small tumor size and/or shallow cancerous invasion into the stomach wall, type IV collagenase activity was higher than that in the cases with lower malignancy (p less than 0.025, p less than 0.05, respectively). These results suggest that collagenase in stomach cancer tissue play an important role in the invasion and metastasis of cancer cells. Type IV collagenase activity in stomach cancer tissue could be one of the useful biological markers for the degree of malignancy.
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PMID:The collagenase activities, interstitial collagenase and type IV collagenase, in human stomach cancer: with special reference to local spreading and lymph node metastasis. 217 1

The formation and propagation of several subpopulations of human melanoma cells from a heterogeneous parental population was accomplished with the use of the Membrane Invasion Culture System (MICS) in vitro under sterile conditions. Five sequentially selected subpopulations of melanoma cells showed an increasing ability to do the following: a) invade reconstituted basement membranes in vitro; b) form experimental lung metastases in vivo; and c) express steady-state levels of human type IV collagenase, a marker for metastatic potential. In addition, the morphology and expression of 35S-methionine-labeled cell surface proteins changed with sequential selection. The adaptation of the MICS assay for studying tumor cell subpopulations allows the morphological, biochemical and molecular characterization of events associated with tumor progression in an in vitro model.
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PMID:Selection of invasive and metastatic subpopulations from a heterogeneous human melanoma cell line. 222 75

Human tissue inhibitor of metalloproteinase-2 (TIMP-2) was cloned and sequenced from an A2058 human melanoma cell cDNA library. When the sequence was compared with that of human TIMP-1 at both the nucleotide and deduced amino acid levels, the homology appeared closer at the protein level than at the nucleotide level, suggesting that these inhibitors diverged early in the evolution of this gene family. Comparison of the deduced amino acid sequence for TIMP-2 with that of human TIMP-1 shows that there are two regions in which the similarity is below the overall average of 66%. It is postulated that these regions are responsible for the unique ability of TIMP-2 to bind to the latent form of the 72-kDa type IV collagenase. Polyclonal anti-TIMP-2 antisera recognized TIMP-2 but not TIMP-1 on immunoblotting. Northern blot analysis of RNA from A2058 human melanoma, HT-144 human melanoma, HT-1080 human fibrosarcoma, and WI-38 fetal lung fibroblast cell lines demonstrated two distinct transcripts of 1.0 and 3.5 kilobases (kb) for timp-2 mRNA. Both transcripts are down-regulated in response to transforming growth factor-beta but are unchanged in response to phorbol ester treatment. This is in contrast to the up-regulation of timp-1 transcripts by these agents and indicates that timp-2 and timp-1 are independently regulated in cell culture. Northern blot analyses of matched normal and tumor tissue samples from five cases of human colorectal carcinoma were performed. Normal and tumor tissues contain both the 1.0- and 3.5-kb transcripts. However, in the tissue samples the ratio of the 3.5-kb transcript to the 1.0-kb transcript was markedly elevated. No evidence of down-regulation of timp-2 transcript levels was noted in the tumor tissues. This is in contrast to the elevated timp-1 transcript levels seen in these tumor samples. Thus, timp-2 mRNA transcript levels are differentially regulated from timp-1 levels in vivo as well as in cell culture.
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PMID:Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. 238 Jan 96

The secretion of a type IV collagen-specific proteinase is stimulated in cultured human skin fibroblasts by the phorbol ester tumor promoter 12-O-tetradecanoyl phorbol 13-acetate (TPA) and during cell proliferation. Exposure of the cells at the late log phase of growth to 10(-9) to 10(-6) M TPA resulted in the secretion of type IV collagenase activity to the medium, this effect being reversible. Incubation of intact type IV procollagen with TPA-induced fibroblast medium protein produced six peptides, four of which corresponded in size to the fragments produced by a type IV collagen-specific collagenase (Fessler, L., Duncan, K., Fessler, J., Salo, T., and Tryggvason (1984) J. Biol. Chem. 259, 9783-9789). The TPA-induced type IV collagen-degrading enzyme could be activated by trypsin, was inhibited by EDTA, but was not affected by soybean trypsin inhibitor, N-ethylmaleimide, aprotinin, or cysteine. Therefore, in human skin fibroblasts, TPA can induce a type IV collagen-specific, metal-dependent collagenase as was previously described in some invasive tumor cells. Furthermore, another metalloprotease is apparently secreted under the same conditions of TPA exposure. The production of metal-dependent, type IV collagen-degrading activity was also studied at different stages of cellular proliferation. In early log phase, a significant amount of enzyme activity was observed in the control cell medium; this activity disappeared during both late log and stationary growth phases. This activity could be markedly increased by the addition of 10(-8) M TPA to the culture medium. The production of matrix-degrading proteinases is therefore likely to be associated with rapid cell proliferation in both transformed and untransformed cells.
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PMID:Tumor-promoting phorbol esters and cell proliferation stimulate secretion of basement membrane (type IV) collagen-degrading metalloproteinase by human fibroblasts. 240 89

Eighty gastric and colorectal lesions including cases of dysplasia and carcinoma were studied by immunohistochemical techniques to investigate the behaviour of laminin, type IV collagen and fibronectin. Their distribution was examined on frozen and formalin-fixed, paraffin-embedded samples. In the same lesions, interruption, fragmentation and absence of basement membrane (BM) antigen-staining were observed. Carcinomas with well differentiated glandular structures were always surrounded by a well defined BM as in normal, non-pathological tissues. On the contrary, undifferentiated areas arranged in nests or sheets were usually negative for laminin and type IV collagen. Anomalous BM staining was strictly related to the degree of differentiation of tumor tissue, while no correlation existed between carcinoma staging and BM antigen presence, either in gastric or colorectal neoplasms. Immunostaining with antibody against type IV collagenase showed a massive positivity in the early gastric carcinomas examined, while in colorectal cancer only granulocytes showed it.
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PMID:Behaviour of basement membrane antigens in gastric and colorectal cancer. Immunohistochemical study. 242 76

The activity of type IV collagenase, which enables tumor cells to degrade collagen type IV found in the subendothelial basement membrane, has been correlated with the metastatic potential in several tumor types, including the rat 13762NF mammary adenocarcinoma cell line and its clones. In this study, we examined whether all-trans-retinoic acid (all-trans-RA) and other retinoids, which exhibit antitumor activity in vitro and in vivo, affect the collagenolytic activity of metastatic rat 13762NF mammary adenocarcinoma cells. Cells of the highly metastatic lung-colonizing clone MTF7.T35.3, derived from the 13762NF cell line, were treated for 3 days with 0.1, 1, or 10 microM all-trans-RA, harvested, and seeded on [3H]proline-labeled extracellular matrix deposited by cultured rat lung endothelial cells or on a film of purified [3H]proline-labeled type IV collagen. The amount of radioactivity released into the medium during the subsequent 24 to 72 h was measured, and it was found that all-trans-RA treatment inhibited degradation of extracellular matrix and type IV collagen by 50 to 60%. This effect was observed whether the cells had been treated with all-trans-RA in serum-free medium or in medium supplemented with heat-inactivated or acid-treated fetal bovine serum. The growth of the cells was not inhibited under these conditions, except after treatment with 10 microM all-trans-RA in serum-free medium. The reduction in collagenolytic activity was observed in viable cells as well as in conditioned medium. A 24-h exposure of cells to all-trans-RA was sufficient to cause a 30% decrease in the collagenolytic activity, and this inhibitory effect was reversible. The direct addition of all-trans-RA to conditioned medium had no effect on secreted collagenase activity. The apparent molecular weights of the collagenolytic enzymes were determined by electrophoresis of cell extracts and concentrated conditioned medium in type IV collagen-embedded polyacrylamide gels followed by renaturation and activation of the enzymes within the gels. Two major type IV collagenolytic metalloproteinases exhibiting molecular weights of 64,000 and 88,000, respectively, were detected by this method. These two enzymes were also found to have specificity for gelatin. The Mr 64,000 enzyme could be extracted from viable cells (presumably from the cell membrane) by 2% 1-butanol. Treatment with all-trans-RA decreased the level of these enzymes in the cellular, cell membrane, and conditioned medium compartments.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibition by retinoic acid of type IV collagenolysis and invasion through reconstituted basement membrane by metastatic rat mammary adenocarcinoma cells. 253 32

The in vivo growth behavior and invasive potential of normal and "immortalized" human bronchial epithelial cells were studied by xenotransplantation procedures, an in vitro assay of invasiveness, and determinations of type IV collagenase activity and mRNA expression. BEAS-2B cells, immortalized after hybrid virus infection (adenovirus 12-simian virus 40), reconstituted a columnar epithelium when xenotransplanted into de-epithelialized rat tracheas transplanted sc into athymic BALB/c mice. A few adenomatous growths could be seen 16 weeks after transplantation. BZR cells, obtained by transfer of the v-Ha-ras oncogene into BEAS-2B cells, were tumorigenic in this xenotransplantation model. BZR-T33 cells, obtained from a tumor produced after injection of BZR cells, were also tumorigenic; however, they exhibited a shorter latent period. When these same cell lines were injected sc and iv into athymic BALB/c mice, BEAS-2B cells were not tumorigenic, and the BZR-T33 cells were more tumorigenic than the BZR cells. The incidence of spontaneous metastases after sc inoculation was zero for BEAS-2B cells, 33% for BZR cells, and 100% for BZR-T33 cells. Similar increasing values that correlated well with the data on in vivo growth were noted in the in vitro invasion assay, the collagenolytic ability, and the mRNA expression of type IV collagenase. Normal human bronchial epithelial cells showed the lowest values in all the assays. These progressive changes occurring in cells derived from the same parental line indicate that the presence of the v-Ha-ras oncogene in immortalized bronchial cells is associated with a full-fledged malignant phenotype, which is further enhanced by in vivo passaging.
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PMID:Invasive and metastatic potential of a v-Ha-ras-transformed human bronchial epithelial cell line. 253 88

Recent studies have shown that the cyclooxygenase and the 5-lipoxygenase pathways of arachidonic acid, are required for the invasive and metastatic activity of certain tumor cells. We show here that malignant murine melanoma and human fibrosarcoma cells cultured in media supplemented with eicosapentaenoic acid show a dose and time dependent decrease in invasiveness, in collagenase IV production and in the case of the murine cells, a reduced ability to metastasize to the lung after intravenous injection. It was also shown that a metabolite of eicosapentaenoic acid was less potent than the comparable arachidonic acid metabolite in restoring collagenase IV production and invasiveness after inhibition of the lipoxygenase pathway. These studies indicate that such supplements have the potential to reduce the metastasis of certain tumor cells, converting them to benign status.
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PMID:Eicosapentaenoic acid reduces the invasive and metastatic activities of malignant tumor cells. 254 5

The goal of this study has been to identify and characterize metalloproteinases from a highly metastatic human small cell lung cancer cell line. The cytosol isolated from NCI-H82 lung cancer cells propagated as solid tumors in nude mice contained a gelatinolytic enzyme that was subjected to ammonium sulfate precipitation, zinc chelate Sepharose column chromatography, anion exchange chromatography and gel permeation chromatography. This purification scheme resulted in a 280-fold enrichment of an active gelatin and type IV collagen-degrading enzyme. On gelatin zymography two bands of gelatinolytic activity were detected, corresponding to Mr of 75,000 and 63,000. Gelatinolytic activity was inhibited by metal chelators, tetracyclines, and serum. On immunoblotting using an affinity-purified polyclonal rabbit antibody to a peptide region of type IV collagenase, the tumor enzyme was identified as type IV collagenase. A second tumor metalloproteinase of Mr = 29,000, which degraded proteoglycan substrates, was also isolated.
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PMID:Gelatin-degrading type IV collagenase isolated from human small cell lung cancer. 254 76


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