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)

When injected i.v. into mice, the F10 subline of B16 melanoma cells produced significantly more lung tumours over a 3-week period than cells of the F101.r-6 subline. However, in animals bearing intramuscular tumours produced by these sublines, the high pulmonary-colonization potential of the F10 cells was not realized, and no significant differences in natural pulmonary metastasis formation were observed in animals with untreated primary cancers, even when they progressed to the moribund state. Massage of i.m. tumours derived from the two sublines produced no change in metastasis and no changes in the numbers of cancer cells in the blood detectable by bioassay. In contrast, massage increased metastasis from tumours derived from an invasive BL6 subline and B16 wild-type cells and, in the case of the wild-type, the numbers of circulating cancer cells. In vitro experiments show that blood cells from non-tumour-bearing animals are toxic to both sublines; but less to F10 than to F101.r-6. In addition, after i.v. injection of radiolabelled cells, more of the F10 subline were retained in the lungs of recipients than the F101.r-6. In spite of these apparent metastatic advantages of the F10 subline following intravasation, the incidence of natural metastases from i.m. F10 and F101.r-6 tumours was similar, suggesting that substantially fewer F10 than F101.r-6 cells gained access to the circulation. Thus, the higher colonization potential of the F10 cells was not matched by its intravasation potential, since metastatic efficiency is determined by the least efficient step in the metastatic process.
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PMID:Metastatic inefficiency in mice bearing B16 melanomas. 705 64

Chromatin structure, in terms of higher order nuclear-DNA condensation (scanning cytometry) and in terms of acridine orange primary binding sites (flow cytometry), is analyzed and shown to be significantly different between high (B16-F10) and low (B16-F1) metastatic variants of B16 melanoma. Furthermore, double staining of B16-F10 and B16-F1 with ethidium bromide (chromatin) and fluorescamine (membranes) provides the identification of a homogeneous subpopulation of cells with enhanced metastatic potential based on differential fluorescamine uptake. Fluorescamine uptake and poststaining viability is shown to be dependent upon the dye/cell ratio at which staining occurs. Utilizing a sterile cell sorting technique, a subpopulation of B16-F10 with increased fluorescamine uptake representing 30% of the total "intact cell" population was isolated by means of a fluorescence activated cell sorter and replated in vitro. This subpopulation when assayed in vivo produced significantly more pulmonary metastases than its parent cell line. Scanning cytometry of the Feulgen stained sorted subpopulation reveals that the cells possess a unique nuclear morphometry characterized by a 2C-3C DNA content and a large nuclear area (disperse chromatin). Finally, when we assay simultaneously for nuclear-DNA organization and cell membrane organization a progressive uncoupling between nuclear and cell morphometry is apparent if B16-F10 (versus B16-F1).
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PMID:Biophysical identification and sorting of high metastatic variants from B16 melanoma tumor. 707 1

Actinomycin D was tested in an experimental preparation to determine its efficacy in the prevention of intravenous metastases. B16 melanoma cells were injected intravenously in syngeneic C57/BL6 mice. Two cell lines of the tumor, designated F1 and F10, with widely different metastatic potentials, were maintained in tissue culture and utilized for evaluation of pulmonary metastases. When actinomycin D was given intraperitoneally at doses of 0.05 and 0.075 mg/kg for 5 days, the number of pulmonary metastases was significantly decreased (P less than .001) in both the F1 and F10 cell lines. Although reduction did occur with a single dose, maximum reduction of pulmonary metastases was effected with a dose schedule administered over 5 days. Evaluation of a group of mice 2 and 3 wk after injection of tumor cells revealed that the effects of actinomycin D were not secondary to delay in tumor growth but did represent highly significant differences in numbers of metastatic lesions. It is concluded that in this experimental preparation actinomycin D, given in an adjuvant setting, can significantly reduce the number of pulmonary metastases. This study may have bearing on the design of adjuvant intraoperative and perioperative chemotherapy in order to destroy circulating tumor cells.
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PMID:Prevention of intravascular metastases of B16 murine melanoma: adjuvant chemotherapy with actinomycin D. 708 84

B16 mouse melanoma sublines cultured in vitro spontaneously shed intact vesicles of plasma membrane. These vesicles can be fused with the plasma membrane of cells from homologous and heterologous B16 sublines using polyethylene glycol (PEG) and phytohemagglutinin (PHA). The ability of FI cells to arrest in the lung and form metastases in this organ is significantly increased by fusion of vesicles from a highly metastatic subline (F10) that localizes exclusively in the lung with cells from another subline (F1) which is poorly metastatic and produce few lung metastases. In contrast, fusion of F1 vesicles with F10 cells does not reduce their ability to localize in the lung of form lung metastases. Vesicle-treated F1 cells revert to their original arrest behavior and metastatic capacity following removal of F10 vesicle components from the plasma membrane. The changes in the arrest and metastatic behavior of F1 cells induced by F10 vesicles are highly specific. Vesicles from other B16 sublines which show limited abilities to localize in the lung (F1, F1(1r) and F10(1r) fail to modify the arrest behavior of F1 cells. These results suggest that the differences in the ability of the F1 and F10 sublines to localize in the lung are determined by differences in surface properties.
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PMID:The influence of cell surface properties on the arrest of circulating melanoma cells. 719 63

A murine melanoma variant (B16-F10ir6), resistant to lymphocytic cytolysis, has been shown previously to produce lower numbers of tumor nodules in the lung of C57BL/6J mice following i.v. inoculations. These differences found in tumor implantation and lymphocyte recognition may be due to changes in surface properties of this cell line. Therefore, membrane-bound sialic acid (released by Vibrio cholerae neuraminidase treatment), ectosialyltransferase activity, and total cellular glycosidase levels were measured in this cell line and compared with levels in its parent melanoma tumor cell line, B16-F10, which was selected for its enhanced ability to form tumor nodules. The results of these studies indicate a correlation between the degree of lung implantation and the amount of tumor cell sialic acid accessible to neuraminidase cleavage, tumor cell surface sialyltransferase activity, and several cellular glycosidase activities. These results are consistent with the idea that membrane structural changes in the glycocalyx may account for the ability of a tumor cell to implant and metastasize.
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PMID:A correlation between cell surface sialyltransferase, sialic acid, and glycosidase activities and the implantability of B16 murine melanoma. 723 26

The role of the host immune response in the abatement or prevention of tumor metastasis is unclear. To investigate possible interaction of lymphocytes with tumor cells, the F10 subline of the B16 melanoma was studied after subcutaneous or intravenous injection in original host C57BL/6 mice, Swiss nude mice, and BALB/c nude mice. The F10 tumor grew rapidly after subcutaneous injection in all strains of mice. Although florid pulmonary metastases were detected in the lungs of C57BL/6 mice after intravenous inoculation, both strains of nude mice were markedly resistant to the development of pulmonary metastases (P less than 0.001). Labeling of the B16 F10 melanoma cells with 3H-thymidine demonstrated that the kinetics of tumor cells after intravenous inoculation were similar in C57BL/6 mice and nude mice. Increased natural killer (NK) activity in the nude mouse play an important role in the prevention of pulmonary metastases.
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PMID:Resistance to intravenous tumor metastases in the athymic nude mouse: a paradoxic response. 725 37

The correlation between the production of plasminogen activator (PA) of tumors and their metastatic potential was studied. B16 melanoma cells and "B16 mets" cells (harvested from the pulmonary metastatic nodules of C57BL/6J mice bearing B16 isografts) were examined with respect to their fibrinolytic activity (FA) in tissue culture. B16 mets cells had a significantly higher FA than did B16 cells. F1 (a B16 subline with a lower incidence of metastasis) and F10 (a highly metastatic B16 subline) were also studied. F10 cells produced more FA than did F1 cells. The difference between the FA's of these tumors was due to differences in their PA production. Significant differences in PA production between F1 and F10 could be consistently observed when 10(5) or more cells were cultured for at least 24 hr. The cell-free supernatants harvested from 72-hr cultures of F10 cells had a higher FA than those harvested from F1 cultures. Results suggest that a quantitative difference in PA production between these 2 melanoma sublines does exist and that it may contribute to their different metastatic potential.
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PMID:Correlation of the production of plasminogen activator with tumor metastasis in B16 mouse melanoma cell lines. 735 11

New assay methods have been devised to quantitate tumor cell invasion of tissues of differing histological complexity maintained as organ cultures in vitro (chorioallantoic membrane of chicken, mouse urinary bladder, and canine blood vessel. In addition to quantitating tumor cell invasion, these methods also allow recovery of invasive cells for comparison with noninvasive cells. These methods have been used to select variant sublines from murine B16-F1 and B16-F10 melanoma lines that display significantly greater tissue-invasive abilities than the parent lines. B16 variant sublines selected in vitro for increased invasiveness through the bladder wall or vein also show a significant increase in their ability to form spontaneous and experimental metastases in vivo. In contrast, cells from the same parent cell line selected for increased invasiveness through the chorioallantoic membrane do not show significant alterations in metastatic behavior. We conclude that invasive variants can be isolated from the parent B16 tumor by several in vitro methods and that the level of expression of the invasive phenotype in vivo may be determined by the severity of the selection procedure in vitro.
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PMID:In vitro selection of murine B16 melanoma variants with enhanced tissue-invasive properties. 737 Sep 95

The spreading and colonization of tumor cells require their migration to metastatic sites via blood vessels. To penetrate blood-vessel walls, cells, including malignant ones, must recognize and associate with the sub-endothelium extracellular matrix (ECM) and its glycoproteins. Recognition of ECM-glycoproteins, such as fibronectin (FN) and vitronectin (VN), is mediated by integrin receptors expressed on various cell types, including platelets, leukocytes and tumor cells. The Arg-Gly-Asp (RGD)-containing peptide, a major adhesive ligand of ECM, is present in various plasma and matrix glycoproteins, such as FN and VN. Non-peptidic mimetics of RGD, consisting of carboxylate and guanidinium groups of Asp and Arg divided by a linear atom spacer, express a high affinity for the alpha IIb-beta 3 integrin and inhibit platelet aggregation. Herein, the ability of RGD mimetics to inhibit adhesive interactions between tumor cells and RGD, and tumor progression in vivo, was examined. RGD-containing peptides and the RGD mimetic, compound SF-6,5, but not the Arg-Gly-Glu (RGE) peptide or the corresponding mimetic, specifically inhibited B16-F10 melanoma cell adhesion to immobilized VN and FN. Daily administration in vivo of SF-6,5 to mice inhibited the formation of B16-F10 colonies in experimental and spontaneous models of metastases. Moreover, SF-6,5 could prevent mouse death caused by massive colonization of tumor cells in the lungs. The therapeutic effect of RGD-containing peptides on tumor metastasis formation was marginal, probably due to the small amounts used, and its susceptibility to proteolysis in situ. Thus, non-peptidic mimetics of small adhesive epitopes may provide a novel therapeutic tool to prevent an adverse pathological event involving integrin-dependent cell-cell and cell-ECM interactions.
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PMID:Inhibition of metastatic cell colonization in murine lungs and tumor-induced morbidity by non-peptidic Arg-Gly-Asp mimetics. 750 56

A major problem in evaluating the effectiveness of tumor cell vaccination and other biological therapies is the variability of experimental models. In this study we have further developed and characterized a model for metastatic melanoma that approximates the major clinical stages of metastatic dissemination: stage I--growth of the primary (local) tumor, stage II--dissemination to regional lymph nodes, and stage III--metastasis to distant organs (lungs). C57BL/6 mice were challenged subcutaneously with B16 F10 murine melanoma cells in the midtail, and within 3 weeks 100% of the mice had local tumors growing in their tails. By 5-7 weeks after challenge, most of the mice had developed metastases to the inguinal lymph nodes and subsequently had metastatic colonies in the lungs and in the bone marrow. Preimmunization of mice with a formalinized extracellular antigen vaccine, derived from B16 F10 melanoma cells, provided partial inhibition of the growth of the primary melanoma tumors, as well as reducing the number of metastases to the regional (inguinal) lymph nodes and lungs along with concomitantly increasing survival time. This model for melanoma metastasis provides a reasonable and reproducible test system for the study of anti-melanoma immunity and the different cellular and humoral mechanisms involved.
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PMID:Further characterization of a clinically relevant model of melanoma metastasis and an effective vaccine. 760 May 58


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