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)

In order to quantify the invasiveness of melanoma tumor cells in vitro, a modification of the amniotic basement membrane (BM) model, described by Liotta et al. (Cancer Letters, 11, 141, 1980), was used in combination with radiolabeled tumor cells. B16-F10 metastatic murine melanoma cells and a derived clone (B16-F10L) were prelabeled with 0.1 muCi/ml of [14C]thymidine for 20-24 h in serum-free medium at 37 degrees C. Following incubation, fetal bovine serum was added to a concentration of 5 per cent, and the cells were allowed to grow to confluency for the next 24-28 h. The labeled cells were seeded onto amniotic membranes situated in Membrane Invasion Culture System (MICS) chambers at a density of 2.5 X 10(4) per well. At various times points, radioactivity of tumor cells that completely traversed the membrane was determined using an under-the-membrane sampling method. The average percent invasion demonstrated by the B16-F10 line was 2.75 per cent, and 3.65 per cent exhibited by the B16-F10L cell line after 48-53 h in vitro. Since it was apparent that some variability in thickness existed among membrane samples, a morphological analysis was performed on five sectors of a three-inch-diameter sample from four different placentae. Differences and similarities in BM thickness within the same sector were noted by this technique and could possibly contribute to some variability observed in tumor cell invasion in this model. Another parameter examined was the proliferation of tumor cells in the upper and lower wells of the MICS chambers. By 48 h, approximately 32.1 per cent of the B16-F10 cell line as well as the clone had replicated in the upper wells associated with the BMs compared with a 32.9 per cent replication in the lower wells, which reaffirmed the viability of the tumor cells under experimental conditions and insured similarly replicating populations of cells. In order to quantify the invasiveness of radiolabeled tumor cells accurately through a biological membranous barrier, the proper concentration of cells must be used, tumor cell heterogeneity should be taken into consideration, the technique of sampling radiolabeled invasive cells should be critically analysed, and thickness of the membranous barrier should all be considered as possible important factors in the quantitative analyses.
Clin Exp Metastasis
PMID:In vitro quantification of melanoma tumor cell invasion. 407 11

The data presented suggest that F1 and F10 cells display an inverse relationship between their levels of metastasis and prostaglandin D2 production. Prostaglandin D2 was able to reduce in vitro aggregation of platelets from C57 black mice. Other prostaglandins that decreased platelet aggregation such as prostacyclin also reduced the metastatic rate. Prostaglandin D2 also reduced macrophage cytotoxicity for B16 target cells in vitro. Interferons stimulated prostaglandin D2 synthesis in F10 cells and reduced lung metastasis. F10 metastasis was not blocked by interferon to the same extent by in vivo treatment as it had been in vitro, suggesting that interferons and other modulators of cell function have broader activity in vivo than simply increasing the level of prostaglandins being produced by metastatic cells. Metastasis can therefore be viewed as being modulated in vivo by several mechanisms that may include platelet aggregation and elimination of metastasized cells by host defenses such as macrophages. Prostaglandins and other naturally occurring modulators of host resistance, such as interferons, appear to affect the metastatic rate of tumor cells. Although prostaglandin D2 is not a common major AA product of most cells and therefore may not operate in all cell systems, the B16 cells may provide a system to address the importance of these mediators and mechanisms in the metastatic process.
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PMID:Prostaglandins and metastasis. 620 37

The purpose of these studies was to establish a procedure for determining the relative experimental metastatic potential of unrelated murine tumors. We used three tumors (the B16-F10 melanoma, which is syngeneic to the C57BL/6N mouse, and the K-1735 melanoma and the UV-2237 fibrosarcoma, which are syngeneic to the C3H/HeN mouse). Various numbers of tumor cells were injected into normal or immunosuppressed syngeneic recipients and into 3-week-old BALB/c nude mice. At appropriate intervals, the recipient mice were killed, and the metastatic burden was determined. The number of experimental metastases was not linearly correlated with cell input. Thus, simply comparing the incidence of metastasis resulting from the injection of one predetermined dose of tumor cells did not allow for determination of their relative metastatic capacities. More reproducible and meaningful results were obtained by introducing increasing numbers of viable tumor cells admixed with a constant number of nontumorigenic (X-irradiated) tumor cells serving as carrier. The incidence of metastasis by few or many injected cells is influenced by host factors such as immune status, and therefore determinations of the true metastatic nature of any given tumor necessitate the choice of an appropriate recipient.
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PMID:Comparative studies on the quantitative analysis of experimental metastatic capacity. 629 61

Reactivity of B16 melanoma cell surface proteins with antisera to the major envelope glycoprotein, gp70, of murine leukemia viruses was assessed by radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Surface proteins from cultured monolayers of the B16 melanoma and variant lines B16-F1, B16-F1(1r6), B16-F10, and B16-F10(1r6), and from purified B16 melanoma tumor cells, contained three glycosylated components specifically reactive with gp70 antisera, with apparent molecular weights of 70,000, 80,000, and 85,000 (B16-gp70, B16-gp80, and B16-gp85). Antisera raised in syngeneic C57BL/6 mice by immunizing with X-irradiated B16, B16-F10, or B16-F10(1r6) cells immunoprecipitated only solubilized B16-gp70, B16-gp80, and B16-gp85. Absorption of mouse antiserum to B16-gp70/80/85 antigens with purified viruses from various sources indicated that antigens on all three molecules were related to endogenous AKR-type murine leukemia virus antigens. Mice hyperimmunized against melanoma cells were challenged subcutaneously with 4 X 10(4), 10(5), or 2.5 X 10(5) viable B16 or B16-F10 cells, inocula that were lethal and nonmetastatic in unimmunized mice. The lowest cell dose was rejected by 90% of immunized mice. Tumors grew in an average of 58% of immunized mice challenged with 10(5) cells, pulmonary metastases occurring in 61% of those mice. Inocula of 2.5 X 10(5) cells grew in all immunized mice, with a 60% incidence of metastasis. These studies indicate that host immunity to B16-gp70/80/85 antigens can either inhibit or stimulate B16 melanoma tumor progression.
Invasion Metastasis 1984
PMID:Multiple antigens related to the major envelope glycoprotein of murine leukemia virus expressed on B16 melanoma cells as targets of host immune response. 632 88

Natural killer (NK) cells are hypothesized to provide resistance against tumors in vivo. The NK system was examined in vivo by the hematogenous dissemination of a murine melanoma in normal C57BL/6 mice (control, athymic homozygous Balb-C nude mice (with increased NK cells), and C57BL/6 beige mice (with decreased NK cells). The highly metastatic F10 subline of the B16 melanoma was maintained in tissue culture to assure high NK sensitivity of the cells. Aliquots of B16-F10 cells in NaCl were injected into the tail vein of 6- to 8-week-old normal mice, nude mice, and beige mice. The mice were killed at 2 weeks and pulmonary nodules were counted under the dissecting microscope. Nude mice were highly resistant to metastases, even at overwhelming doses. Beige mice, however, developed significantly increased numbers of metastases at low doses as compared with control mice (p less than 0.001). We conclude that NK cells serve an important function in the control of tumor metastasis in this in vivo animal preparation. Further investigation of modulation of the NK system in this preparation may elucidate benefits for the treatment of cancer in man.
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PMID:Abrogation of hematogenous metastases in a murine model by natural killer cells. 646 54

The effect of a human recombinant hybrid alpha interferon (referred to as rHuIFN-alphaA/D) on pulmonary metastases induced by intravenous injection of B16 F10 melanoma cells in C57BL/6 mice was examined; rHuIFN-alphaA/D has been previously shown to have anti-viral, anti-proliferative and immunomodulatory activities in murine cells. Pretreatment of mice with 4 daily intraperitoneal injections of rHuIFN-alphaA/D resulted in a marked decrease in the number of pulmonary metastases. This inhibition was dose-dependent but was not seen when mice were similarly treated with rHuIFN-alphaA, a human recombinant alpha interferon subtype which is inactive on murine cells. Treatment of mice with rHuIFN-alphaA/D following B16 F10 injection resulted in no significant inhibition of pulmonary metastases. Mice given a similar treatment regimen of rHuIFN-alphaA/D had elevated natural killer (NK) cell activity as measured by in vitro cytotoxicity against YAC-I or in vivo pulmonary clearance of B16 F10 cells. Pretreatment of mice with 10 daily injections of rHuIFN-alphaA/D resulted in decreased NK activity and less inhibition of metastases. Therefore, in this model system, rHuIFN-alphaA/D inhibits metastases when given in the appropriate treatment schedule. Furthermore, the data are consistent with the hypothesis that rHuIFN-alphaA/D-induced inhibition is a consequence of the immunomodulation of NK cells, which prevent the establishment of pulmonary metastases.
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PMID:Inhibition of experimentally-induced murine metastases by recombinant alpha interferon: correlation between the modulatory effect of interferon treatment on natural killer cell activity and inhibition of metastases. 648 Jan 58

An attempt has been made to determine (a) whether aging plays an important role in resistance against metastasis and (b) whether dithiothreitol, an effective in vitro mitogenic potentiator of splenic cells of young and old mice, can modulate the occurrence of pulmonary metastasis. B16-F10 melanoma cells were injected into the outer ear of young and old female C57BL/6 mice; and the growth of the primary tumor, the palpable size of the cervical lymph node, and the number of lung metastases were then determined at various intervals. The ear was amputated when the primary tumor reached 4 mm in mean diameter. The following results were obtained. (a) The growth rate of the primary tumor in young mice is comparable to that in old mice. (b) Enlargement of the cervical lymph node occurs earlier in old than in young mice. (c) Old mice are more vulnerable to pulmonary metastases, but small metastasized pulmonary colonies are more prominent in old than in young mice. (d) Dithiothreitol (100 micrograms) injected every 2 days after the inoculation of tumor cells is effective in reducing the incidence of pulmonary metastases in old mice.
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PMID:Different metastatic modes of malignant melanoma implanted in the ear of young and old mice. 656 76

Tumor metastasis was examined after iv inoculation of highly metastatic variants of mouse tumors. Highly metastatic variants, B16-F10 and B16-BL6, of B16 melanoma origin and colon 26 NL-17 of colon adenocarcinoma 26 origin were used in the experiments. Formation of pulmonary metastasis was influenced by the mouse strain and age. Based on the results, experimental metastasis systems of these tumors were established, and the effects of chemotherapeutic agents were examined. 5-Fluorouracil and adriamycin were significantly effective for the suppression of pulmonary metastasis. The degrees of suppression of metastasis by these drugs were different with different tumor variants, but the sensitivity of the metastasis to the drug was similar to that of the parent tumor. Several aspects of the chemotherapy of metastasis are discussed.
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PMID:Metastasis after intravenous inoculation of highly metastatic variants of mouse tumors and the effects of several antitumor drugs on the tumors. 673 31

B16 mouse melanoma sublines in culture spontaneously shed intact plasma membrane vesicles. These vesicles can be fused with the plasma membrane of cells from homologous and heterologous B16 sublines by using polyethylene glycol and phytohemagglutinin-P. Fusion of vesicles from a highly metastatic subline (F10) that localizes exclusively in the lung with cells from a poorly metastatic subline (F1) significantly increased the ability of F1 cells to become arrested in the lung and form metastases in this organ. In contrast, fusion of F1 vesicles with F10 cells did not alter the ability of vesicle-modified cells to localize in the lung or form lung metastases. F10 vesicle-modified F1 cells reverted to their original arrest behavior and metastatic capacity after removal of F10 vesicle components from the plasma membrane. The changes in the arrest and metastatic behavior of F10 vesicle-modified F1 cells were highly highly specific. Vesicles from other B16 sublines that are poorly metastatic and show limited localization in the lung (F1, FLLr, and F10Lr) did not modify the arrest behavior and metastatic capacity of FU cells. These results suggest that the differences in the abilities of the F1 and F10 sublines to localize in the lung are determined by differences in cell surface properties.
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PMID:Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells. 692 31

The effects of treatment with colchicine, cytochalasin B, and low temperature (4 degrees C) on the metastatic behavior of the B16-F10 melanoma cell line were examined. The growth of metastases and the distribution of radiolabeled tumor cells were monitored in inbred C57/BL6 mice given iv injections of B16-F10 cells. Cells treated previously with both drugs, but not with low temperature, produced fewer lung nodules than did control cells and displayed alterations in tumor dissemination patterns. In vitro studies revealed that both drugs reduced the rate of adhesion of the tumor cells to bovine endothelial cell monolayers, the rate of migration from agarose droplets, the formation of homotypic aggregates, and agglutination by wheat germ agglutinin. The drugs also induced morphologic alterations of the cells grown in monolayer culture but had little effect on cell volume.
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PMID:Effect of cytoskeleton-disrupting agents on the metastatic behavior of melanoma cells. 692


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