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

The highly malignant/metastatic murine large cell lymphoma cell line RAW117-H10 forms 100-200 times more liver metastatic tumors than its parental counterpart cell line RAW117-P. RAW117-H10 cells, but not the less malignant/metastatic parental cells, significantly inhibited the mitogen-induced proliferation of normal syngeneic Balb/c and allogeneic ICRC mouse spleen cells. Such an inhibition also occurred when mitomycin-C treated metastatic lymphoma cells were added 24 h after initiation of culture, indicating that no competition with mitogen binding sites on the lymphocytes was necessary for inhibition of proliferation. 'Antiproliferative' cell surface molecules were extracted non-cytolytically from the RAW117-H10 cells using butanol. The butanol extracts from the metastatic RAW117-H10 cells also inhibited the mitogen-induced proliferation and natural killer (NK) cell-mediated cytotoxicity of normal spleen cells. Our results indicate that these 'antiproliferative' cell surface molecules of metastatic murine RAW117-H10 lymphoma cells may have important role(s) in tumor-mediated host immunosuppression.
Clin Exp Metastasis
PMID:Enhanced antiproliferative activity by metastatic RAW117 lymphoma cells. 201 14

Recognition of the carbohydrate part of cellular glycoconjugates by cell-surface sugar receptors may contribute to interactions, essential to the establishment of metastases. Comparison of the properties of strongly metastatic variants to their related, less metastatic counterparts offers a generally accepted approach to the discovery of metastasis-associated characteristics. The chemically induced murine lymphoma line Eb and its spontaneously arising variant ESb with increased potential for lung and liver colonization, the virally induced lymphosarcoma cell line RAW117-P and its in vivo selected variant H10 with increased potential for liver colonization, and the B16-F1 melanoma line and its in vivo selected variant F10 with increased potential for lung colonization, were chosen. A panel of 12 types of chemically glycosylated E. coli beta-galactosidase, exposing the pivotal carbohydrate residues for specific carbohydrate-dependent cell binding, was employed to study the expression of respective cell-surface sugar receptors on these cell lines. Specific binding occurred in a non-uniform manner for the individual probes. Systematic measurements at a non-saturating ligand concentration revealed quantitative differences between the 2 cell lines of each system. However, there were no consistent changes associated with the metastatic phenotype. A similar result was obtained employing Scatchard analyses for quantitative evaluation of binding characteristics in several cases. Surface receptor expression was responsive to chemical induction of differentiation in the lymphosarcoma model. Analyses of sugar-inhibitable cell adhesion to neoglycoprotein-coated plastic wells for the lymphoma and lymphosarcoma cells revealed that the presence of cell-surface sugar receptors, even at similar densities to those defined by neoglycoenzyme binding, will not necessarily translate into an identical adhesive response. Several carbohydrates, especially N-acetyl-D-galactosamine, can differentially affect this interaction at a non-toxic concentration in both model systems.
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PMID:Analysis of cell-surface sugar receptor expression by neoglycoenzyme binding and adhesion to plastic-immobilized neoglycoproteins for related weakly and strongly metastatic cell lines of murine tumor model systems. 216 45

The adhesive, invasive, and growth properties of parental murine large-cell lymphoma cells of low metastatic potential (RAW117-P) were compared to in-vivo-selected sublines of high metastatic potential to liver (RAW117-H10) or lung (RAW117-L17). Using small (approximately 0.5 mm3) pieces of syngeneic organ tissue (lung, liver, kidney) we found that RAW117-L17 cells selectively attached to and invaded lung tissue, whereas RAW117-H10 cells preferentially attached to and invaded liver tissue. We measured adhesion to microvessel endothelial cells established from syngeneic lung and liver and found that the RAW117-L17 cells bound to lung microvessel endothelial cells at significantly higher rates than the other lines, and RAW117-H10 and -L17 cells attached to hepatic sinusoidal endothelial cells at significantly faster rates than RAW117-P cells. Such organ specificity of adhesion was not found at the level of the subendothelial matrix, and the rates of adhesion of RAW117 cells to subendothelial matrix were lower than to endothelial cells. RAW117 cells of low or high metastatic potential bound to immobilized extracellular matrix components, such as fibronectin, at high rats, but adhesion to laminin or collagen IV was minimal. Previous studies indicated that RAW117 lines could proliferate in vitro in certain organ-conditioned media under limiting serum conditions. We therefore examined the ability of a purified paracrine lung growth factor (LDGF-1) to stimulate growth of RAW117 cells in limiting serum-containing medium. The high lung-colonizing L17 line was stimulated to proliferate by LDGF-1 at faster rates than the other lines. The data support Paget's hypothesis that the organ specificity of tumor metastasis is determined by specific tumor cell and host properties.
Invasion Metastasis 1989
PMID:Adhesive, invasive, and growth properties of selected metastatic variants of a murine large-cell lymphoma. 270 4

A syngeneic murine model system was used to study the immunobiology of metastasis. The highly malignant RAW117-H10 cell line was compared to the less malignant parental RAW117-P cell line from which it was derived, for expression of cell surface antigens. Using rabbit antisera, two major glycoprotein antigens were detected on the tumor cell surfaces. Antigen-I was uniformly distributed over the surface of these cells whereas antigen-II had a patchy, punctate distribution. Antigen-I was displayed less on RAW117-H10 cells than on RAW117-P cells, while the expression of the other serologically distinct antigen (antigen-II) was increased on RAW117-H10 cells compared to the less malignant parental (RAW117-P) cells. This differential antigen expression was assessed by immunodiffusion, a 125I-labeled protein-A binding assay, flow cytometry and rocket immunoelectrophoresis. Both these antigens had a molecular weight of 70,000 daltons. Antigen-I bound the lectin concanavalin-A whereas antigen-II did not, suggesting that antigen-I might be the viral envelope glycoprotein gp70. The identity of antigen-II is presently unknown. Syngeneic Balb/c mice injected with highly malignant and metastatic RAW117-H10 cells coated with antiserum to antigen-I were protected from early death; this effect was not seen with RAW117-H10 cells coated with antiserum to antigen-II. The opsonizing qualities of these antisera may be different due to antibody to antigen-II being shed more rapidly than antibody to antigen-I.
Clin Exp Metastasis
PMID:Characterization of metastasis-associated antigens on RAW117 lymphosarcoma cell lines. 310 62

Using a low metastatic potential parental (P) line of the murine large cell lymphoma RAW117 and a highly metastatic in vivo-selected liver-colonizing subline (H10), we examined the relationship between cell surface glycoprotein expression and metastasis. The highly metastatic H10 cells showed loss of the major RNA tumor virus envelope glycoprotein gp70 and increased expression of a concanavalin A and Lens culinaris hemagglutinin (LcH)-binding glycoprotein of Mr approximately 15,000 (gp150) by lectin affinity chromatography and 125I-lectin staining of isolated RAW117 glycoproteins. When the amounts of cell surface LcH-binding components were determined on P and H10 cells, the mean amount of cell-bound LcH on H10 cells was significantly greater than on P cells. RAW117-P cells were sorted for low (PLcH-low) or high (PLcH-high) LcH binding using a fluorescence-activated cell sorter, or for binding to immobilized LcH, and the resulting cell sublines were analyzed for their metastatic properties by intravenous injection into BALB/c mice. The parental P cells formed few liver tumor nodules (median 0; range 0-8), as did the PLcH-low cells (median 0; range 0), whereas the high LcH-adherent P cells and the cells sorted for increased LcH binding, PLcH-high, were highly metastatic to the liver (median 200; range 156 to 200+). Analyses of gp150 and gp70 contents indicated higher amounts of gp150 but lower quantities of gp70 on PLcH-high cells than on PLcH-low or P cells. The results suggest that the amounts of cell surface gp150 and gp70 are important in determining the metastatic properties of RAW117 cells.
Invasion Metastasis 1988
PMID:Cell surface biochemical and metastatic properties of Lens culinaris hemagglutinin-binding variants of a murine large cell lymphoma. 326 5

Many cancers display characteristic organ colonization patterns that do not fit simple, anatomical-mechanical trapping theories of tumor cell dissemination. Organ preferences of metastatic spread appear to be mediated partly by the selective attachment of tumor cells to organ-specific, microvascular endothelium. To study these tumor cell-endothelial cell interactions in an efficient and reproducible manner, we have designed a novel in vitro assay system wherein endothelial cells isolated from large vessels (e.g., aorta) can be modulated to assume phenotypic traits of organ-specific, microvascular endothelium. Modulation is achieved by growing bovine aortic endothelial cells (BAEC) on organ-specific matrix components, termed tumor attachment modulators (TAMs). Using monolayers of modulated BAEC in a tumor attachment assay, we show here that tumor cells which metastasize to a given organ, have a significantly higher binding affinity for BAEC grown on TAMs of the preferred, metastasized organ, than they have for BAEC grown on TAMs of any other organ not colonized by these tumor cells. Lung-metastatic tumor cells (R3230AC-MET, B16-F10) adhere preferentially to BAEC monolayers grown on lung-specific TAMs, whereas liver-metastatic tumor cells (RAW117-H10, M5076) selectively adhere to BAEC grown on liver-specific TAMs. In contrast, nonmetastatic tumors cells (R3230AC-LR, RBTCC-1, 647V) show no such adhesion preferences. Preferential tumor cell adherence is increased by growing BAEC for prolonged periods on organ-specific TAMs. Metastatic preference and organ distribution are mediated, at least in part, by urea-extractable endothelial cell surface components that are regulated by the extracellular matrix.
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PMID:Organ preference of metastasis. The role of organ-specifically modulated endothelial cells. 335 32

The Abelson-virus-induced murine lymphosarcoma cell line RAW117-P and its in vivo selected highly malignant and metastatic variant RAW117-H10 have been studied for their growth in vivo, in vitro and in semi-solid agar. The highly malignant metastatic variant RAW117-H10 cells killed syngeneic Balb/c mice rapidly and formed 100-200 times more gross liver tumor nodules than the less malignant parental RAW117-P cells. On the other hand, there were no differences between the in vitro growth kinetics of these cells as measured by various parameters such as metaphase arrest or cells in DNA synthetic phase on various days after the initiation of the culture. These cells could be grown in semi-solid agar and formed characteristic colonies. The parental cells formed many very small colonies, whereas the highly malignant cells formed fewer, but very large colonies in soft agar. These results suggest that differential interactions of highly malignant RAW117-H10 cells with the host, particularly the host immune system, are much more important for regulating the number of metastases than any intrinsic growth advantages. It appears that growth differences, potentially based on lack of response to feedback inhibition rather than on kinetic parameters, are responsible for highly malignant RAW117-H10 cells forming larger colonies both in agar in vitro and in the liver in vivo.
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PMID:Differential growth characteristics of low and high metastatic variant RAW117 murine lymphosarcoma cells. 360 20

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

Metastatic variant sublines of the murine RAW117 large cell lymphoma or lymphosarcoma have been established in vitro by sequential cycles of harvesting of liver tumor nodules after intravenous inoculation of tumor cell suspensions into syngeneic BALB/c mice. After five and ten in vivo selections for liver colonization, variant sublines RAW117-H5 and -H10, respectively, were established, and these formed significantly more surface liver tumors than the parental RAW117-P line. RAW117 sublines were tested for their abilities to adhere to embryonic mouse liver or brain cells in an in vitro cell-cell adhesion assay. Liver colonizing RAW117-H10 cells adhered with greater selectivity to liver cells than to brain cells. Parental RAW117-P cells were more homotypically adhesive, but they were nonselective in their organ cell adhesion properties. We examined RAW117 cells for the presence of liver cross-reactive antigens using polyclonal xenoantibody preparations directed against embryonic murine liver cells. These antibody preparations block organ-specific homotypic adhesion of embryonic murine liver cells in vitro. The amount of fetal liver antigen(s) expressed on RAW117 sublines correlated with liver colonization potentials (H10 greater than H5 greater than P) in quantitative absorption assays. Treatment of the highly metastatic RAW117-H10 subline with polyclonal anti-embryonic murine liver F(ab')2 or Fab' antibody fragments had no effect on RAW117-H10 cell viability or growth in vitro or in vivo, but inhibited liver colonization (median liver tumor colonies reduced from greater than 200 to 0) and prolonged life expectancy. In contrast, pretreatment of RAW117-H10 cells with polyclonal anti-H-2 did not modify the in vivo biologic properties of these metastatic cells.
Clin Exp Metastasis
PMID:Involvement of cell-cell adhesion molecules in liver colonization by metastatic murine lymphoma/lymphosarcoma variants. 654 50

Poorly liver metastatic large-cell lymphoma RAW117-P cells were sequentially selected in vitro for increased adhesion to murine hepatic sinusoidal endothelial cells. After three or four sequential selections, the selected sublines showed increased rates of adhesion to target hepatic microvessel endothelial cells and increased formation of experimental metastases in the liver. However, the endothelial cell adhesion-selected RAW117 sublines were generally unstable and gradually lost their enhanced adhesive and metastatic properties during passage in culture. Highly metastatic, liver-selected RAW117-H10 large-cell lymphoma cells were more resistant to the cytostatic effects of interferon-gamma (IFN-gamma) than poorly metastatic unselected parental RAW117-P cells. When tested for their sensitivity to IFN-gamma, the endothelial cell adhesion variants were significantly more resistant than the unselected RAW117-P cells, but after a 72-h treatment with IFN-gamma, the in vitro-selected cells lost their enhanced endothelial cell adhesion characteristics, their potential to colonize the liver, and their ability to grow when injected at subcutaneous or intramuscular sites. In contrast, the metastatic potential of similarly treated RAW117-P cells was unaffected by IFN-gamma during a 72-h treatment. Sequential selection of RAW117-P cells for increased resistance to IFN-gamma in vitro resulted in variant lines that were refractory to the growth-inhibiting effects of IFN-gamma, and these IFN-gamma-selected variants were also less adhesive to liver microvessel endothelial cells. The IFN-gamma-selected variants also lost their experimental metastatic potentials completely and their tumorigenicities at sites of subcutaneous or intramuscular injection. Cytofluorographic analysis indicated reduced cell surface expression of H-2Kd antigen and fibronectin receptor on the selected variant cells but no change in cell surface mu heavy chain immunoglobulin. The unselected and selected RAW117 lines had similar sensitivities to natural killer (NK) cell-mediated cytolysis, indicating that the in vivo differences were probably not due to differences in NK cell-mediated cytolysis. The results suggest that selection for adhesion to organ microvessel endothelial cells or sequential exposure to certain cytokines can affect the adhesive, growth and metastatic properties of RAW117 cells without modifying their responses to NK cells.
Clin Exp Metastasis 1993 Nov
PMID:Selection for enhanced adhesion to microvessel endothelial cells or resistance to interferon-gamma modulates the metastatic potential of murine RAW117 large-cell lymphoma cells. 822 95


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