Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several angiogenic preparations that have been shown to stimulate plasminogen activator (PA) and collagenase production by cultured bovine capillary endothelial (BCE) cells were tested for their ability to stimulate BCE cell motility in the phagokinetic track assay. Bovine retinal extract, medium conditioned by 3T3-F442A differentiated mouse adipocytes, SK HEP-1 human hepatoma cell lysate, mouse sarcoma 180 cell lysate, and medium conditioned by mouse sarcoma 180 cells stimulated motility 68.7%, 48.5%, 140.9%, 56.5%, and 102.1%, respectively, relative to untreated cells. The motility-stimulating activity of these preparations was dose dependent and linear over the 16-h assay period. Several hormones and growth factors were tested for BCE cell motility-stimulating activity, including insulin, vasopressin, fibroblast growth factor, and a partially purified preparation of sarcoma growth factor, and were found to be ineffective. 12-0-tetradecanoyl-phorbol-acetate (TPA), a potent stimulator of both PA and collagenase activities in BCE cells, also did not stimulate motility, indicating that protease production is not sufficient to stimulate BCE cell motility in this assay. Neither SK HEP-1 hepatoma cell lysate nor TPA was effective in stimulating motility in bovine aortic endothelial (BAE) cells. The inability of SK HEP-1 hepatoma cell lysate to stimulate movement in BAE cells is consistent with the observation that angiogenesis occurs by sprouting of capillaries, not large vessels.
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PMID:Stimulation of motility in cultured bovine capillary endothelial cells by angiogenic preparations. 632 76

Serial transplantation of a spontaneous BDX rat tumor, classified as an anaplastic sarcoma, gives rise to two variants; a rapidly growing nonmetastatic line (AS) and a slowly growing, invasive, and highly metastatic variant (ASML). The availability of two cell lines of the same origin but with markedly differing metastatic potential offers an ideal model for the identification of the cellular properties involved in invasive and/or metastatic behavior. The present work focuses on the pattern of various proteinases in the two tumor cell variants. The findings disclosed one major consistent difference which relates to a cathepsin B-like cysteine proteinase. The metastatic ASML variant manifests exceedingly high intracellular cathepsin B-like activity; in the nonmetastatic AS variant, the activity of this proteinase is significantly lower. Other proteinases, in particular elastase-like, chymotrypsin-like, collagenase-like enzymes and plasminogen activator, showed low, essentially comparable activity patterns. Thus, cathepsin B-like proteinase is a marker enzyme of the metastatic ASML tumor cell variant.
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PMID:Cathepsin B-like proteinase as a marker for metastatic tumor cell variants. 638 97

The effect of natural protease inhibitors and a chemoattractant on tumor cell invasion were studied with the use of a new in vitro quantitative assay of tumor cell penetration of native connective tissue. Human amnion membrane denuded of its epithelium is composed of a continuous basement membrane (BM) attached to a dense avascular collagenous stroma. M5076 reticulum sarcoma cells, known to be highly invasive in vivo, were placed on the BM side of the amnion connective tissue. Tumor cells penetrating the full thickness of the connective tissue barrier were collected on the stromal side with a Millipore filter. N-Formylmethionyl-leucyl-phenylalanine (FMLP) at an optimal concentration of 10(-7) M stimulated the penetration of up to 600% more tumor cells into the connective tissue after 20 hours in comparison to the number of tumor cells spontaneously penetrating in serum-free media. Natural protease inhibitors blocked both FMLP-stimulated and spontaneous invasion. A bovine cartilage extract containing inhibitors of both serine proteinases and metalloproteinases caused a 500% decrease in invasion. Furthermore, a 500% inhibition of invasion was produced by a purified collagenase (metalloproteinase) inhibitor. In contrast, soybean trypsin inhibitor and bovine serum albumin did not significantly alter the invasion rate. The protease inhibitors were nontoxic and did not reduce tumor cell proliferation, attachment to the amnion, and the rate of tumor cell migration through Nuclepore filters. These data support the hypothesis that collagenolytic metalloproteinases play a necessary role in tumor cell invasion of native connective tissue.
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PMID:Effect of natural protease inhibitors and a chemoattractant on tumor cell invasion in vitro. 675 21

Certain metabolic properties of hormonally responsive osteogenic sarcoma cells derived from a transplantable rat tumor have been compared with those of related normal rat bone cells. All studies were carried out on cells grown in monolayer culture. Normal rat bone cells derived by repeated collagenase/trypsin digestion of newborn rat calvaria. Bone cells selected for comparison were thought to be osteoblast-like, as judged by enrichment of alkaline phosphatase and adenylate cyclase responsiveness to parathyroid hormone and prostaglandin E2. The adenylate cyclases of the two cell strains were similarly stimulated by a range of prostanoids and their metabolites and analogs. Morphology showed the two cell strains to be similar; the only obvious difference was a multilayering of cells in the sarcoma cultures, while the normal cultures showed abundant extracellular fibril formation which was not seen in the tumor cells. Investigation of the cAMP-dependent protein kinase isoenzymes showed the presence of two forms in both cell types, one eluting at a low salt concentration and the other at a high salt concentration. There was approximately twice the amount of the first isoenzyme compared to the second isoenzyme. The results indicate the usefulness of the two cell strains to elucidate further the molecular mechanisms of action of parathyroid hormone and prostaglandins.
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PMID:Functional properties of hormonally responsive cultured normal and malignant rat osteoblastic cells. 693 60

Moloney sarcoma-virus (MSV)-induced tumours in A/Sn mice have been dispersed with collagenase and DNase 8-15 days after virus inoculation, and both "sarcoma" and inflammatory cells separated by sedimentation velocity and adherence techniques. The isolated "sarcoma" cells had the morphological characteristics of atypical cells (i.e. cytoplasmic blebbing, vacuolization and prominent nucleoli) and were easily adapted to in vitro growth. As few as 2 x 10(3) of these cells inoculated i.m. produced new tumours within 8 days of injection in both syngeneic and allogeneic mice. Also, cell-free supernatant from "sarcoma"-cell cultures produced tumours, indicating that the successful transplantation of the "sarcoma" cells was probably due to production of infective virus. Cells cytotoxic in vitro against the "sarcoma" cells were present within both spleen and tumour of the tumour donors, but not in the spleens of normal mice. The cytotoxicity was specific against virus-infected cells, since in a mixture of virus-positive (gp 70) and virus-negative cells, positive cells were removed while negative cells were not affected, as measured by a visual cytotoxicity assay using immunostaining. Although T cells could be isolated from the MSV-induced tumours, these cells did not appear to mediate the cytotoxicity detected against the MSV "sarcoma" cells. These results suggest that early MSV infections might be sensitive to cytotoxic mechanisms distinct from those reported with established MLV- or MSV-induced tumour lines.
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PMID:In vitro demonstration of in situ autologous tumour-cell cytotoxicity in MSV-induced tumours in A/SN mice. 705 11

In this paper the recognition of various rat tumor cells by rat liver cells is demonstrated in vitro. A liver cell receptor involved in the binding process has been identified. The ultrastructure of the cell contacts was examined by transmission electron microscopy. Hepatocytes and Kupffer cells were isolated from rat liver by collagenase treatment and cell adhesion tests were performed with 4 different tumor cells types. Hepatocytes were found to bind Walker sarcoma cells, lymphoma cells and Yoshida hepatoma cells but not leukemia 5222 cells. Kupffer cells bound all tumor cell types. Normal blood cells were not bound under the same conditions. Recognition of tumor cells by hepatocytes was mediated by a galactose specific lectin on the liver cell surface as shown by hapten inhibition experiments with specific saccharides. Although Kupffer cells express a similar lectin-like receptor adhesion of tumor cells could not or only slightly be inhibited by galactose or related saccharides. It is concluded that the spontaneous adhesion of tumor cells to liver cells in vitro is a specific recognition event which in part is mediated by lectin-carbohydrate interactions.
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PMID:Galactosyl specific receptor on liver cells: binding site for tumor cells. 728 63

The biosynthesis of collagen and fibronectin molecules by cultivated glomerular epithelial or mesangial cells was studied at confluency using radioactive proline or lysine as precursors. Collagen represented 0.5% of the total protein synthesized by the glomerular epithelial cells. About 60% of this collagenous protein were associated to the cell layer, whereas about 40% were secreted into the culture medium. Two major collagenous polypeptides were observed with apparent molecular weights of 185K and 170K, and were identified as two gene products of type IV procollagen. They exhibited ratios of 3- to 4-hydroxyproline, of total hydroxyproline to proline, and of hydroxylysine to lysine characteristic of type IV procollagen. They were degraded by bacterial collagenase. The patterns of peptides obtained after digestion of the 185K and 170K chains of this type IV procollagen with pepsin and V8 protease were identical to those obtained after digestion of type IV procollagen chains purified from a murine tumor (EHS sarcoma). Finally. a purified antibody to type IV collagen specifically immunoprecipitated the collagenous protein produced by the glomerular epithelial cells. By contrast, the mesangial cells synthesized about 5% of collagenous protein. 90% of this collagen were secreted into the cultured medium, whereas about 10% remained associated to the cell layer. Type I, III and IV procollagens were synthesized by the mesangial cells. Fibronectin was found in the medium and cell layer of both epithelial and mesangial cells. Fibronectin molecules were identified by their resistance to bacterial collagenase, their susceptibility to pepsin digestion, and their specific adherence to collagen. It was composed of disulfide-linked peptides of 220K daltons. The data therefore demonstrate that: (a) the glomerular epithelial and mesangial cells synthesize fibronectin molecules and type IV procollagen in vitro; (b) the cultivated mesangial cells also synthesize type I and III collagens. The implications of these findings in certain pathological circumstances, such as diabetes mellitus, are now being investigated.
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PMID:Synthesis of collagen and fibronectin by glomerular cells in culture. 732 12

Cancer cachexia has a great impact on morbidity and mortality in patients undergoing surgery. Failure to maintain lean tissue against tumor-induced hypermetabolism results in cumulative weight loss and ultimate failure of the host. Cellular free energy is among the factors that regulates metabolic pathways and may be altered in the tumor-bearing state. We studied in-vivo and in-vitro ATP levels and metabolic parameters in Fischer rats bearing a methylcholanthrene-induced sarcoma to elucidate the energy state. Tissue ATP was measured in freeze-clamped liver and muscle in 15 tumor-bearing rats (TBR) at different tumor burdens and their pair-fed controls (CTR) by bioluminescence assay. Plasma metabolites, hormones, and enzymes were determined in the same animals. Liver ATP level was lower in TBR with a 5% tumor burden: 3.07 +/- 0.56 (SE) nmole/mg tissue vs CTR: 5.33 +/- 0.60 (P < 0.05), 10% TBR: 2.48 +/- 0.54 vs CTR: 4.05 +/- 0.63 (n.s.), and 20% TBR: 1.91 +/- 0.21 vs CTR: 3.86 +/- 0.40 (P < 0.01). Muscle ATP was not different between TBR and CTR. This progressive loss of liver ATP was associated with decreased plasma insulin level (P < 0.001) and with increased alkaline phosphatase level (P < 0.01) by multiple regression. In vitro, hepatocytes were isolated from 8 TBR and 8 CTR by in-situ liver perfusion with collagenase and the cellular ATP was measured before and after 60 min incubation with glucogenic substrates. Hepatocytes from TBR decreased ATP by 42% (P < 0.05) in 10 mM lactate with higher gluconeogenesis, while control hepatocytes maintained the ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Energy depletion in the liver and in isolated hepatocytes of tumor-bearing animals. 756 11

Production of metalloproteinases such as collagenases has been reported to be involved in the metastasis of cancer cells. Granulocytic sarcoma in extramedullary sites can be formed by similar steps to other cancers. In this study, we have examined the secretion of type IV collagenases and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in several human leukemia cell lines, including a granulocytic sarcoma-derived cell line established from a patient with granulocytic sarcomas in dermal tissues. We have also examined the invasive capacity of these leukemia cell lines into reconstituted basement membrane, Matrigel, which was used for in vitro invasion assay. Among the human leukemia cell lines used in this study, only the granulocytic sarcoma cell line was found to secrete type IV collagenase constitutively. Other myeloid leukemia cell lines such as HL-60 and U-937 produced type IV collagenase only after treatment with 12-O-tetradecanoylphorbol-13-acetate. All the cell lines secreted similar amounts of the tissue inhibitor of metalloproteinases. In vitro invasion assay revealed that the granulocytic sarcoma cell line showed higher invasive capacity than the other cell lines. These results suggest that the secretion of 92 kDa type IV collagenase plays a role in the leukemia cells' invasion of extramedullary tissues.
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PMID:A possible role of 92 kDa type IV collagenase in the extramedullary tumor formation in leukemia. 774

We have utilized a newly developed culture system to study the properties of antitumor CD4+ T-cells relevant to the rejection of syngeneic methylcholanthrene sarcomas. Fresh syngeneic dendritic cells prepared from spleen, then pulsed with crude lysates of methylcholanthrene sarcomas, evoke antigen-specific proliferation by CD4+ but not by CD8+ T-cells from tumor-immune mice. Unfractionated splenocytes display similar antigen presenting capacity if they are not irradiated before the pulse with tumor lysate. CD4+ T-cells from mice immunized to individual methylcholanthrene sarcomas proliferate cross-reactively to dendritic cells pulsed with fresh tumor digests, but not to dendritic cells pulsed with cultured tumor cells. This apparent shared recognition of sarcoma lysates was demonstrated to be a result of sensitization to bacterial collagenase during the immunization procedure. Therefore, the murine CD4+ T-cell response to tumor immunization is similar to the CD8+ response in that sensitization occurs predominantly to tumor specific transplantation antigens rather than to shared tumor antigens. Strategies to avoid artefactual tumor cross-recognition by CD4+ T-cells are discussed.
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PMID:CD4+ T-cells from mice immunized to syngeneic sarcomas recognize distinct, non-shared tumor antigens. 790 97


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