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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we report a more detailed biochemical analysis of the B16 melanoma, metastasis-associated, Met-72 antigen. Specifically, we have examined (1) the molecular forms of Met-72 isolated during synthesis, surface expression and 'shedding' and (2) the cell-surface expression of Met-72 during the cell cycle. These experiments show that the 72 kD species originally described has an isoelectric point of between 6.3 and 6.9, but is the desialylated derivative of an 83 kD native molecule whose isoelectric point ranges between pH 4.9 and 5.6. In addition, a 90 kD glycoprotein doublet was immunoprecipitated from biosynthetically labelled B16 melanoma cells, but does not appear to be a precursor of the 83 kD or 72 kD molecule. These findings have led us to interchangeably use the terminology Met-72 and Met 72/83. The latter terminology more accurately describes the physical forms which can be identified by different labelling procedures. When culture supernatants from 3H-leucine labelled cells were subjected to anti-Met-72 immunoprecipitation, a 35 kD species was identified as a possible 'shed' product of these cells. Met-72/83 expression during the cell cycle was analyzed by flow cytometry and found not to be restricted to any particular stage. In addition, experiments were performed to determine whether low levels of Met-72 expression on poorly metastatic B16 melanomal clones was a direct result of low levels of synthesis, or if other control mechanisms regulated intracellular pools of Met-72 prior to cell-surface expression.
Clin Exp Metastasis
PMID:Synthesis and expression of metastasis-associated, Met-72/83 antigens. 340 61

Three lines of B16 melanoma cells (B16-F1, B16-F10 and B16-BL6) were examined for motility in the micropore filter assay and for synthesis in culture of the basal lamina glycoprotein laminin. All three lines synthesized laminin as judged by the incorporation of [35S]methionine into immunoreactive laminin and secreted (or shed) laminin into the culture medium as indicated by biosynthetic labeling studies and enzyme-linked immunosorbent assays. Immunoreactive laminin was also seen on the surface of the cells as indicated by immunofluorescence staining and by complement-mediated killing. Analysis of [35S]methionine-labeled laminin immunoprecipitates by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) both with and without reduction of intersubunit disulfide bonds revealed that all three cell lines produced a similar array of laminin forms, and that the Mr = 950 kD laminin molecule (but not the uncombined subunits) was secreted into the culture medium. Laminin biosynthesis appeared to be limited by the availability of the Mr = 400 kD A subunit as shown by the intracellular accumulation of excess B subunit in the form of uncombined B subunit (Mr = 200 kD) and as a disulfide-linked B dimer (Mr = 400 kD). The motility of all three cell lines was stimulated four- to five-fold by the addition of either exogenous laminin from the EHS sarcoma or culture medium from the B16 cells containing the secreted laminin. The stimulated motility was inhibited by antilaminin serum. These observations suggest that the laminin synthesized by the B16 melanoma cells themselves may facilitate their motility.
Clin Exp Metastasis
PMID:Laminin production by murine melanoma cells: possible involvement in cell motility. 353 34

Two widely used B16 melanoma cell lines of low and high lung colonizing potential (B16-F1 and B16-F10) were compared in their ability to induce platelet aggregation. The results of these experiments showed a reproducible difference in platelet aggregating activity of these two cell lines which directly correlated with their lung colonizing potentials. However, when clones were derived from these heterogeneous cell lines and tested for experimental metastatic potential, platelet aggregating ability and Met-72 expression, no correlation could be attached to the platelet aggregating activity of the clones. Results of these experiments provide direct evidence that platelet aggregation is not an accurate index of experimental metastatic potential of tumor cell clones, nor is it an essential trait of all metastatic cells. The ability of tumor cells to induce platelet aggregation is examined and discussed in the context of cellular heterogeneity.
Clin Exp Metastasis
PMID:The lack of correlation between experimental metastatic potential and platelet aggregating activity of B16 melanoma clones viewed in relation to tumor cell heterogeneity. 359 70

The parent R3230 AC rat mammary carcinoma cell line and the two variant cell lines, R3230 AC MET and R3230 AC LR, differ with respect to their abilities to invade bony matrices and to form lung colonies (experimental metastases). Both the R3230 AC and the R3230 AC MET, a cell line selected in vivo for enhanced metastatic capability, express high potentials for invasiveness and lung colony formation, while the Con A- and WGA-resistant R3230 AC LR cell line grows expansively at the periosseus implantation site and is unable to form lung colonies after intravenous inoculation. The abilities to invade bone and to metastasize to the lung are well correlated with the fibrinolytic activity and the production of urokinase-type plasminogen activators. The contribution of plasminogen activators to invasiveness and metastasis has been ascribed to its role in the fibrinolytic and collagenolytic (i.e., activation of latent collagenase) cascades.
Invasion Metastasis 1987
PMID:Correlation of fibrinolytic activity with invasion and metastasis of R3230 AC rat mammary carcinoma cell lines. 359 83

Many Experimental and human tumor cell lines have been previously described as being dependent upon exogenous methionine for their in vitro proliferation. The rationale of the experiments described herein was to decrease the in vivo growth of malignant tumors by reducing the exogenous methionine available in diets fed to Wistar AG rats bearing the highly metastatic rhabdomyosarcoma, RMS-J1. The methionine content in the diet was reduced either by replacing casein (diet 1) with soybean protein (diet 4), or by lowering the amount of soybean protein in the diet (from 23 g/100 g to 12 g/100g) (diet 5), or by using a crystalline amino acid-defined mixture as the source of protein (diet 7). In the latter diet homocysteine replaced methionine and allowed the survival of the animals. Diet 4 significantly reduced the mean number of lung metastases without affecting the primary tumor growth. Treatment of RMS-J1 bearing rats with diet 5 led to the decrease of pulmonary invasion (78 and 21 median lung metastases, respectively, in control and treated groups). This diminished metastatic dissemination resulted from the reduced methionine consumption: the lowered casein content in diet 3 (10 g/100 g) as compared to diet 1 (23 g) did not alter primary tumor growth or the amplitude of lung invasion. Moreover, the addition of methionine to diet 5 prevented the diminution of the median number of lung metastases. Replacement of methionine with homocysteine in the crystalline amino acid-defined mixture (diet 7) fed to RMS-J1 bearing rats led to a limited retardation of primary tumor growth (less than 10%) and to a significant decrease in pulmonary invasion: the median number of pulmonary metastases was 28 and 9 for control and treated rats respectively.
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PMID:Decreased rat rhabdomyosarcoma pulmonary metastases in response to a low methionine diet. 367 75

Various murine tumour sublines which differed considerably in their in vivo metastatic capacity were tested in vitro for their ability to invade normal tissue. For this purpose we developed two quantitative tests, a Boyden chamber endothelial cell invasion assay and a brain tissue microsphere invasion assay. The invasion of [75Se]methionine-prelabelled tumour cells into the normal tissues was followed by measuring the percentage of tumour-associated label in the brain microspheres or the endothelial monolayers after 12-48 h of co-cultivation. Clear and comparable differences existed in both assays between the amount of radiolabel found in the normal tissues after a co-cultivation with the different tumour lines. In three of the four tumour lines invasiveness correlated with metastatic capacity. The fourth line, a plastic adherent variant, was highly invasive but low metastatic. The ability of tumour cells to invade normal tissue, therefore, while necessary for the generation of metastases, is not in itself sufficient. Since both assays are independent of time-consuming histological sectioning and staining and allow a quantitative determination of invasive capacity of tumour cells grown as single cell suspensions they appear well suited for experimental manipulation and for screening of anti-invasive drugs.
Clin Exp Metastasis
PMID:Quantitative analysis of cancer invasion in vitro: comparison of two new assays and of tumour sublines with different metastatic capacity. 372 58

Analysis of a number of B16 melanoma clones has revealed a high correlation between metastatic activity and the quantitative expression of a 72,000 dalton glycoprotein, Met 72. In the present study, metastatic tumor cell variants have been directly isolated from a heterogeneous, poorly metastatic melanoma (B16-F1) by anti-Met 72 monclonal antibodies and cell sorting procedures. These studies provide direct proof that Met-72 antigens are in fact surface markers of B16 melanoma metastatic variants and may provide the means of monitoring their presence, influence and autonomy during tumor progression.
Clin Exp Metastasis
PMID:Isolation of metastatic B16 melanoma variants using anti-Met 72 monoclonal antibodies and flow cytometry. 382 95

A primary subcutaneous tumour of low spontaneous metastatic capacity, produced after inoculation of Herpes-virus hominis type-2-transformed hamster fibroblasts (parent line) and two in vivo derived highly metastatic lung deposits (Met A and Met B) were karyotyped and compared after trypsin G-banding. The parent line was cytogenetically heterogeneous with a modal chromosome number of 74. However, a number of cells were of a higher ploidy level. A large variation in both numerical and structural abnormalities was observed, the chromosome rearrangements were often complex and unstable, but all the cells contained a theme of common marker chromosomes. Met A and Met B were near diploid (mean chromosome numbers 42 and 44 respectively) with a low level of tetraploid cells. They shared many chromosome rearrangements but could be readily distinguished by an additional translocation unique to Met A. Cytogenetic homogeneity within and between metastases suggested that they were of monoclonal origin and had been derived from a karyotypically similar subpopulation within the parent tumour. We were unable to detect such cells in the parent line; thus, their numbers within the parent tumour were likely to be low. Metastasis, therefore, has been highly selective, depending on the particular phenotypic properties of Met A and Met B. All cells of the parent and metastatic lines have homogeneously staining regions (HSR) and abnormalities of chromosomes 15 (C15) which may be important in tumorigenesis. In addition, Met A and Met B cells have a number of chromosome rearrangements [translocations, deletions and a double minute chromosome (DM)] not present in the parent cells. They are retained at a high frequency in the cells of Met A and Met B and thus it seems likely that the metastatic phenotype is associated with one or more of these chromosome aberrations.
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PMID:Non-random chromosome changes in a herpes-virus-transformed Syrian hamster cell line and its metastatic derivatives. 609 77

The relationship between the expression of a transformation-related cellular-encoded phosphoprotein, p53, and the potential to form distant metastases was investigated in Abelson murine leukemia virus-transformed murine large cell lymphoma sublines of differing metastatic behaviors. Low metastasis RAW117-P and high metastasis RAW117-H10 cells were labeled with 35S-methionine, and several anti-p53 monoclonal antibodies were used to immunoprecipitate p53 from the cell lysates. Using these procedures, similar amounts of p53 were detected in the RAW117-P and -H10 cells. In addition, the expression of 2.0 Kb mRNA containing p53-specific sequences was equivalent in RAW117-P and -H10 cells. The results indicate that p53 expression, although apparently required for neoplastic transformation, is not quantitatively related to metastatic behavior in RAW117 large cell lymphoma cells.
Clin Exp Metastasis
PMID:The expression of transformation-related protein p53 and p53-containing mRNA in murine RAW117 large cell lymphoma cells of differing metastatic potential. 639 97

The effects of variations in the concentrations of L-cystine (Cys), L-methionine (Met), and L-glutamine (Glu) on the establishment of melanocyte cell lines obtained from a primary tumor and its metastasis in the same patient were studied. The special role of Glu was also studied in 4 lymph node metastases from other patients. Differentiation in vitro was dependent on the culture conditions, as assessed by morphologic and biochemical studies. Karyologic expression, doubling time, cloning efficiency, and tumorigenicity in nude BALB/c mice varied widely among the cell lines. Cys was an indispensable amino acid and Glu was not. Met and Glu were implicated in melanogenesis. From these observations arose the question of the accuracy of comparative results, concerning differentiation and tumorigenicity, that had been collected for cell lines obtained under different culture conditions.
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PMID:Differentiation and tumorigenicity of human malignant melanocytes in relation to their culture conditions. 642 May 97


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