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  • 1
    Electronic Resource
    Electronic Resource
    Role of NK cells in tumour growth and metastasis in beige mice (1980)
    [s.l.] : Nature Publishing Group
    Nature 284 (1980), S. 622-624 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] NK cells seem to be pre-T cells that do not require thymic maturation. This could account for their presence in athymic nude mice6. The level of NK cell activity is genetically controlled7, age-dependent8 and may be augmented by numerous agents, including infection with lymphocytic choriomeningitis ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/284622a0
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  • 2
    Electronic Resource
    Electronic Resource
    Response of natural killer cells from dietary tyrosine-and phenylalanine-restricted mice to biological response modifiers (1988)
    Springer
    Cancer immunology immunotherapy 26 (1988), S. 67-73 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of dietary tyrosine and phenylalanine restriction on splenic natural killer (NK) cell activity was studied in tumor-free B6D2F1 and NIH nude mice and in B16 bladder-6 (BL6) melanoma-bearing B6D2F1 mice. This dietary restriction was found to suppress the naturally elevated NK-cell activity of nude mice and to induce a specific lymphocytopenia in B6D2F1 mice fed the restricted diet for a prolonged period. Baseline NK-cell activity was significantly lower in tumor-free B6D2F1 mice fed a diet restricted in tyrosine and phenylalanine (restricted diet) than in tumor-free mice fed a basal diet. Similar kinetics of activation after a single i.p. injection of 100 μg of polyinosinic:polycytidylic acid (poly I:C) were observed in mice fed both diets. NK-cell activity was not significantly augmented after i.v. inoculation of BL6 melanoma, irrespective of the diet fed; however, it was enhanced in tumor-bearing mice after poly I:C injection. This augmentation was similar to that observed in tumor-free mice. Spleen cells from mice fed either diet were responsive to stimulation of NK-cell activity after in vitro incubation with interleukin-2. These results indicate that dietary restriction of tyrosine and phenylalanine, a potentially useful therapeutic adjunct known to lower NK-cell activity, does not significantly interfere with poly I:C or interleukin-2 induction of NK cells. Our results also demonstrate that, while this dietary restriction causes lymphocytopenia, no effect of the diet could be found on total serum IgG or circulating immune complex levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199850
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  • 3
    Electronic Resource
    Electronic Resource
    Immunoselection of tumor variants resistant to antibody-mediated cytotoxicity (1982)
    Springer
    Cancer immunology immunotherapy 14 (1982), S. 124-131 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunological characteristics of two series of metastatic variants of restricted genetic origin were related to their lung-colony-forming potential. A series of metastatic variants was isolated from a tumor-cell population in which heterogeneity appeared following short-term in vivo passage, while a second series of variants were immunoselected in vitro for resistance to antibody-complement-mediated cell lysis. In the case of the first series, the sensitivity of the individual variants to cell-mediated and antibody-complement-mediated cytotoxicity appeared to be partly determined by the number and rate of loss of antibody-binding sites on the cell surface. These characteristics also correlated with the efficiency of experimental metastasis in the animal. We compared the results reported herein with our previous studies of nonimmune parameters for this series of metastatic variants, and we conclude that immunological differences can be important to the efficiency of lung-colony formation. However, in the case of the second series of variants, despite selection in vitro for resistance to antibody-complement-mediated cell lysis, the behavior of these variants in the lung colony assay could not be predicted by the immunologic parameters examined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00200180
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  • 4
    Electronic Resource
    Electronic Resource
    Interaction between specific dietary factors and experimental chemotherapy of metastatic melanoma (1986)
    Springer
    Cancer chemotherapy and pharmacology 16 (1986), S. 229-236 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The single and combined effects of (a) dietary restriction of phenylalanine and tyrosine, (b) levodopa methylester chemotherapy, and (c) megadose sodium ascorbate supplementation on experimental metastasis was determined in B16-BL6 melanoma. Dietary restriction and levodopa methylester therapy inhibited tumor outgrowth, whereas ascorbate alone was inactive. In combination, however, the effect of dietary restriction and levodopa methylester chemotherapy was augmented by sodium ascorbate. Tumor cells surviving this combination therapy (treated population) were isolated from the lungs of treated mice, and proved to be tumorigenic when inoculated SC into the back of naive mice. The resulting tumors grew more slowly than those produced by inoculation of similarly isolated control cells (control population), irrespective of whether the diet was adequate or deficient in phenylalanine and tyrosine. Failure of the treated tumor cell population to exhibit reduced sensitivity to the combination chemotherapy or, unlike the control population, to exhibit variation in pigmentation levels, suggests that the restriction of phenylalanine and tyrosine during drug therapy alters the tumor response to reduce heterogeneity and perhaps interferes with the emergence of drug resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293983
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  • 5
    Electronic Resource
    Electronic Resource
    Immunologic enhancement of experimental metastasis in the rat (1984)
    Springer
    Cancer immunology immunotherapy 17 (1984), S. 42-50 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using a series of immunologically cross-reactive metastatic tumor variants, we demonstrate that serum from animals bearing pulmonary tumor colonies possesses enhancing properties in the experimental metastasis (lung colony) assay. Enhancement is produced by chronic serum administration and promotes the growth of tumor cells arrested in the lungs which would not otherwise proliferate to form grossly detectable lung nodules. Tumor-bearer serum from animals with lung colonies derived from the most highly metastatic variant examined is shown to possess enhancing properties in both BD-IX(H-1d) and BD-IV(H-1d) rat strains, while tumor-bearer serum from animals with lung colonies derived from the less metastatic parent tumor cell line possesses enhancing properties in the BD-IX rat strain only. Removal of immunoglobulin from enhancing serum by affinity column chromatography simultaneously removes the enhancing factor(s), and enhancing activity correlates with the presence of increased levels of Clq-binding immune complexes in the serum. Serum levels of immune complexes are shown to be more elevated in serum from animals bearing lung colonies derived from the most highly metastatic variant. The enhancing moieties are shown to bind to concanavalin A, but not to staphylococcal protein A, and the active fraction elutes from concanavalin A-Sepharose with α-methyl-mannoside. Consideration of immunoprecipitation studies on whole and fractionated enhancing sera, along with studies on affinity purified isotype fractions reveals that the activity resides with antibodies of IgG2b subclass.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205496
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  • 6
    Electronic Resource
    Electronic Resource
    Control pathways of the 67 kDa laminin binding protein: surface expression and activity of a new ligand binding domain (1995)
    Springer
    Clinical & experimental metastasis 13 (1995), S. 357-372 
    Details
    ISSN: 1573-7276
    Keywords: laminin ; 67 kDa laminin binding protein ; metastatic potential ; peptide 11 ; solid tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: A number of papers have been published on the clinical correlation of the expression of the 67 kDa laminin binding protein (LBP) with the metastatic potential of solid tumors. Both mRNA and protein expression levels have been reported, but both the relationship between them and the molecular nature of the 67 kDa surface product remain unclear. We have utilized a homotypic overexpression system to investigate the cell surface presentation of the 67 kDa LBP and the contribution of this protein to the invasive phenotype of cultured cell lines. We report here that the cellular mRNA levels do not directly reflect the levels of the 67 kDa LBP observed on the cell surface in this overexpression system. Methotrexate amplification of transfected plasmids expressing the 67 kDa LBP leads to an initial elevation of both the LBP mRNA and surface protein levels. This is accompanied by an altered, more flattened, cell morphology. Later, apparent adaptation of the cells to methotrexate is accompanied by a down-regulation of the surface expression of the protein. mRNA levels, however, remain elevated. A nine amino acid sequence, CDPGYIGSR (peptide 11), within the β chain of laminin 1 has been identified as a probable binding domain for the 67 kDa LBP. Previous studies have identified a region of the 67 kDa LBP which may be involved in laminin interaction, although not necessarily via the peptide 11 domain. We have identified a second site within the amino acid coding sequence of the 67 kDa LBP which also shows biological activity both in vitro and in vivo. A peptide with this sequence, LBP residues 205-229, binds laminin-1 in a peptide 11 inhibitable manner. The receptor-derived peptide modulates invasion of basement membrane matrix in vitro and inhibits experimental lung colony formation when injected along with B16BL6 mouse melanoma cells. However, pretreatment of the melanoma cells with the peptide enhances lung colony formation. Thus, the interaction of the 67 kDa LBP with basement membrane matrix appears to involve a complex series of events including multiple adhesive sites and tight regulation of cell surface expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00121912
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  • 7
    Electronic Resource
    Electronic Resource
    Cell-matrix interactions during tumor invasion (1990)
    Springer
    Cancer and metastasis reviews 9 (1990), S. 113-123 
    Details
    ISSN: 1573-7233
    Keywords: cellular adhesion ; motility ; invasion ; extracellular matrix
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This manuscript reviews the molecular aspects of tumor cell invasion of extracellular matrix. The changes in cell:substrate and cell:cell receptors that characterize motile cells are discussed for their importance not only in mediating invasive cell behavior, but also as diagnostic markers for invasive potential. Autocrine motility and scatter factors probably have key roles in initiating migratory behavior, while specific and non-specific extracellular matrix alterations can facilitate cell locomotion. The manuscript reviews reported changes, such as induction of cell motility, matrix degrading enzymes, and invasive/metastatic potential, which can follow transfection with ras oncogenes, and details the key roles of metalloproteinases, heparanase, and plasminogen activator in matrix degradation. Enzymatic inhibitors of initial steps in extracellular matrix degradation, such as rTIMP, and synthetic blockers of adhesive steps in tumor cell invasion represent types of reagent with potential as anti-metastatic agents. Their potential usefulness may be increased if they can be incorporated into a novel, long-term, non-traditional delivery system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00046338
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  • 8
    Electronic Resource
    Electronic Resource
    Comparison of basement membrane matrix degradation by purified proteases and by metastatic tumor cells (1987)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 35 (1987), S. 31-49 
    Details
    ISSN: 0730-2312
    Keywords: basement membrane ; extracellular matrix degradation ; metastasis ; collagen type IV ; laminin ; glycosaminoglycan degradation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: We have examined the nature of biochemical degradation of an isolated basement membrane matrix (bovine lens capsule) using different methodologies. The first strategy was quantitation of the release of surface-bound 125I and a second the documentation by SDS-PAGE of the appearance of putative cleavage products and the loss of high-molecular-weight components from the matrix. Basement membrane matrix bands resolved on SDS-PAGE were identified by their protease sensitivities as well as by Western immunoblots using monoclonal antibodies developed for this study. Radioiodinated components were found predominantly at positions on the gel equivalent to 160-200 kd and 400 kd proteins. Since these labeled moieties were sensitive to bacterial collagenase digestion and stained with anticollagen type IV antibodies, they were determined to represent various configurations of collagen type IV. Several other lower-molecular-weight bands also stained with the anticollagen IV antibodies. Monoclonal antibodies reactive with laminin exhibited a complex staining pattern on the gels, which included the expected 200 and 400 kd components. We confirmed that lens capsule basement membrane contained only a single heparan sulfate glycosaminoglycan species, and tumor cell-induced glycosaminoglycan degradation within the basement membrane matrix was detected using cellulose acetate electrophoresis.Distinctive putative cleavage products were resolved on SDS-PAGE gels from matrices subjected to digestion by a variety of purified proteases as well as by metastatic tumor cells or their conditioned media. Tumor cells of different histio-types produced different characteristic cleavage patterns, suggestive of the existence of several pathways of matrix degradation. Overall, primary tumor cells exhibited a greater degradative activity towards the basement membrane matrix than did long-term tissue culture-passaged cells. The same tumor cell line could exhibit considerably different patterns of both protein and glycosaminoglycan degradation depending on recent culture history. The relevance of these biochemical studies to the pathogenesis of malignant neoplasms is shown by: (1) the evaluation of degradative activities of B16 tumor cell populations exhibiting enhanced lung-colonizing phenotypes, and (2) the ability of a known antimetastatic moiety with antiproteasc activity (Haementeria leech species salivary gland extract) to protect matrix components from degradation by tumor cell-conditioned medium.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240350104
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  • 9
    Electronic Resource
    Electronic Resource
    Introduction of metastatic heterogeneity by short-term in vivo passage of a cloned transformed cell line (1979)
    New York, N.Y. : Wiley-Blackwell
    Journal of Supramolecular Structure 12 (1979), S. 227-243 
    Details
    ISSN: 0091-7419
    Keywords: cloned hepatic cell line ; isolation of metastatic variants ; metastatic heterogeneity introduced by ascites passage ; metastatic homogeneity and stability ; quantitative lung colony assay ; scanning electron microscopy ; tumor cell arrest and survival ; Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: An experimental system for the study of metastasis has been developed using an epithelioid cell line of hepatic origin which had previously been chemically transformed in vitro. These metastatic cells were studied in the syngeneic rat strain. The cloned parent cell line metastasizes only to the lungs following in travenous, subcutaneous, or intraperitoneal injection. The metastatic phenotype is stable during in vitro passage, and subclones from the parent clone have a metastatic capacity statistically similar to that of the parent clone. Following ascites passage of the parent cell line, the cell population obtained exhibits the same metastatic ability as the parent clone. However, subclones obtained from the ascites-passaged population exhibit metastatic heterogneity. This heterogeneity is introduced by the host passage and not by in vitro culture or subcloning. In the case of the two metastatic variants examined, the difference in the metastatic phenotype is found not to be due to differences in arrest or trapping of the cells but appears to be related to long-term survival and proliferation of the tumor cells following their arrest in the lungs. Morphologically the variants are very similar, and growth of the metastatic foci provokes a vigorous inflammatory response by the host.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jss.400120208
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  • 10
    Electronic Resource
    Electronic Resource
    In vitro characteristics of metastatic variant subclones of restricted genetic origin (1981)
    New York, NY : Wiley-Blackwell
    Journal of Supramolecular Structure and Cellular Biochemistry 15 (1981), S. 139-151 
    Details
    ISSN: 0275-3723
    Keywords: metastatic variants ; in vitro correlates ; rat ; Chemistry ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: We have studied several metastatic variant cell lines derived from a common clonal origin and their transformed and untransformed parental cell lines. A number of in vitro characteristics were examined for each tumor line and these properties were correlated with the ability of the tumor cells to form pulmonary nodules in an experimental metastasis assay.Direct correlations with metastatic behavior in the lung colony assay were found to exist with the amount of cell-bound Concanavalin A and the procoagulant activities of cell lysates. In vitro parameters that did not correlate with the metastatic phenotype were: population doubling times in culture, saturation density achieved in culture, the number of colony-forming cells shed from confluent cultures, rates of cellular attachment to homotypic or heterotypic cell monolayers, plasminogen-activator production and procoagulant activity produced in serum-free conditioned medium.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jsscb.1981.380150205
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