Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The availability of neoplastic cell lines with well defined growth characteristics has greatly facilitated study of the tumor phenotype, tumor progression and metastatic process. MmB16 cell line has been established in vitro from the B16 mouse melanoma serially passaged in C57BL/6 mice. From MmB16 cells two lectin-resistant (LecR) variants were selected with the use of Aleuria aurantia agglutinin (AAA). The correlation between the lectin resistance and their in vivo growth parameters, especially tumorigenicity and metastatic ability, were evaluated. The local tumor growth and the average survival time of mice after subcutaneous (s.c.) inoculation of AAAR variant cells did not differ significantly from those of the parent MmB16 cells. However, the AAAR variants revealed significantly higher experimental lung colonizing ability after intravenous (i.v.) administration and slightly increased spontaneous metastatic ability after s.c. inoculation, as compared to parent MmB16 cells.
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PMID:Tumorigenicity and metastatic ability of MmB16 mouse melanoma cell line and its two Aleuria aurantia agglutinin resistant variants. 134 Jan 80

Bladder tumor cell lines derived from male F344 rats treated with N-buthyl N-(4-hydroxybuthyl) nitrosamine (BBN) or N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) have been established in vitro and characterized with respect to histology, karyotype, myc and c-Ha-ras oncogene expression or mutation, anchorage-independent growth and tumorigenicity in nude mice. This unique model system comprising 13 cell populations was employed to study common events during development of carcinogen-induced urothelial neoplasia. Differential expression of malignant phenotypes by these cell lines prompted us to examine their expression of carbohydrate structures binding peanut agglutinin (PNA), soy bean agglutinin (SBA) or leukoagglutinin (L-PHA), which are known indicators of tumor progression in rodents and humans. In the present study we analyzed the patterns of glycoproteins reactive with PNA and L-PHA by Western blotting. We also estimated quantitative differences in lectin binding to surfaces of normal rat urothelium and tumor cell lines by flow cytometry. The patterns of PNA or L-PHA reactive glycoproteins expressed by tumor cells were different from that of normal urothelium in culture. They were also different amongst the tumor cells. A unique non-sialylated, PNA binding glycoprotein (117 kD) was seen in the case of the highly tumorigenic F5 cell line and absent in normal urothelium as well as in other tumor cell lines. Normal cells did not express glycoprotein 60 kD binding PNA (only after desialylation), which was found in lysates of some but not all transformed cell lines. A very high molecular weight (much greater than 200), perhaps mucin-like sialoglycoprotein was found in normal urothelium but not in most of the tumor cell lines. Four major L-PHA reactive bands (greater than 200, 190, 100, 80 kD approximately) were found in normal urothelium. Some of those bands were overexpressed or missing in materials isolated from different tumor cell populations. Total cell surface binding of SBA and PNA by different tumor cell lines was very heterogenous (167-2% that of normal urothelium). No simple correlation between expression of the lectin binding glycoconjugates by urothelial carcinoma cells and other known functional, phenotypic or genetic alterations was found. We were also unable to demonstrate carcinogen-specific changes in expression of lectin binding to these tumor cell lines. Thus we conclude that lectin binding patterns are cell line specific. This may reflect distinct pathways of progression of individual cell lines. The potential sources of phenotypic variability between the cell lines were discussed.
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PMID:Cell line specific abnormalities in expression of PNA, SBA and L-PHA binding sites by carcinogen induced rat urothelial carcinomas. 152 17

The T-antigen system and the mean nuclear volume have been proposed as risk variables in bladder tumors. This study includes 34 patients with initially noninvasive (Ta) transitional cell carcinomas who experienced different courses of disease. Tissue specimens of primary tumors were analyzed for the expression of T-antigen, Tn-antigen, and sialosyl-Tn-antigen using monoclonal antibodies (MoAb) and the lectin peanut agglutinin (PNA) in an indirect immunoperoxidase method. In addition, the mean nuclear volume was estimated by morphometry. Tissue from 7 of 13 patients (54%) who had invasive disease during a follow-up period of 5 years expressed T-antigen, as defined by MoAb HH8 in the primary tumor, whereas tissue of only 3 of 21 patients who did not have invasive disease expressed the antigen (P less than 0.02). No association was found between tumor progression to invasion and the expression of Tn-antigen or sialosyl-Tn-antigen. Tn-antigen expression was partially lost in invasive tumors (P less than 0.03) when compared with the expression in primary noninvasive tumors. A high mean nuclear volume in tissue specimens of primary tumors correlated with a progression to invasive disease (P less than 0.01). A significantly (P less than 0.003) higher mean nuclear volume was found in tumor areas that were positive for PNA compared with areas that were negative for PNA in primary tumors. A significantly lower mean nuclear volume was found in Tn-antigen-positive invasive Grade 3 tumor areas than in Tn-antigen-negative areas (P less than 0.005). The combined use of T-antigen expression and mean nuclear volume is of potential clinical interest for determining patients who are at high risk of disease progression.
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PMID:Nuclear volume and expression of T-antigen, sialosyl-Tn-antigen, and Tn-antigen in carcinoma of the human bladder. Relation to tumor recurrence and progression. 172 66

A recently established model for local breast cancer recurrence using the 13762NF rat mammary adenocarcinoma was used to evaluate biologic and biochemical properties related to clinical outcome for this class of tumors. Sublines isolated from local tumor regrowths following surgical resection differed from each other and from the 'parental' cell lines for multiple phenotypes, including metastatic propensity. Local recurrence- and primary tumor-derived sublines were examined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), lectin binding to electrophoretically separated proteins, and lactoperoxidase-catalyzed cell surface iodination; and differential protein patterns were compared to tumor progression and metastatic potential. 2D-PAGE revealed several quantitatively different spots which correlated with lung colonization potential. In particular, quantities of an apparently unique, non-cell-surface protein, P50.9 (Mr approximately 50,900, pI approximately 7.3) correlated inversely with metastatic propensity, suggesting that it may be associated with, among other possibilities, the negative regulation of the metastatic phenotype. P50.9 was unrelated to four similarly sized metastasis-associated proteins--tumor autocrine motility factor; the rat analog of tumor suppressor, p53; rat cytokeratin 14 or procathepsin D--as determined by amino acid analysis. A major wheat germ agglutinin binding sialoglycoprotein, gp93 (Mr approximately 93,000), was present in smaller amounts as cells were passaged in vivo and re-established as in vitro cultures [MTF7 greater than 'primary' tumor-derived lines (sc1, sc3) much greater than local recurrence-derived lines (LR1, LR1a, LR3, LR4, LR5, LR6)]. Besides cell surface glycoprotein losses, two of six local recurrence-derived sublines expressed a wheat germ agglutinin-binding sialoglycoprotein, gp110 (Mr approximately 110,000), previously undetected on any of the other cell lines including the parental populations. gp110 was found in LR3 and LR6 which were relatively highly metastatic; however, correlation with metastatic potential failed because gp110 was not present on the metastatic parental cell line, MTF7. These results demonstrate specific quantitative and qualitative protein differences associated with the selection of locally recurrent mammary tumors.
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PMID:Tumor progression- and metastasis-associated proteins identified using a model of locally recurrent rat mammary adenocarcinomas. 222 68

We examined 35 cases of stomach carcinoma and 40 cases of colonic carcinoma with PNA associated with peroxidase (peanut agglutinin, lectin which binds to the terminal disaccharide galactose beta (1,3)-N-acetil-galacto-samine). In this way evaluation of the functional aspects of the normal-neoplastic sequence was undertaken. This method was carried out for histological and ultrastructural investigations. The results obtained in both cases showed a different reactivity in the evolution of neoplastic disease: in fact, positivity in dysplasia is finely granular intracytoplasmic, whereas in well-differentiated neoplastic transformation such a reactivity is preferentially localized along the cellular membranes, with restoration of gross positivity in the cytoplasm for the poorly-differentiated neoplasm. We therefore believe PNA to be a marker not only of neoplastic progression but of differentiation as well: we also hypothesize it to reveal glycoprotein groups with possible antigenic power, involved in immunologic interactions between tumor and host.
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PMID:PNA: a marker of neoplastic progression and differentiation in the gastro-intestinal tract. 228 82

Normal adult human melanocytes grown either in the presence of phorbol ester or dialyzed hypothalamic extract were analyzed for their cell surface sialic acid and galactose content. In both cases, cells expressed large amounts of sialic acid, whereas they differed in their terminal nonreducing beta-D-galactosyl residues linked to N-acetyl galactosamine; such residues were accessible to peanut agglutinin and Bauhinia purpurea lectin on cells grown in phorbol ester and inaccessible on cells grown with dialyzed hypothalamic extract. In addition, striking differences in morphology and growth characteristics were observed between adult melanocytes grown with phorbol ester or with dialyzed hypothalamic extract. Thus, pure cultures of normal adult human melanocytes grown in the presence of dialyzed hypothalamic extract displayed cell surface properties different from those of melanocytes grown with phorbol ester. Cultures of melanocytes with dialyzed hypothalamic extract are likely to reflect known cell surface characteristics of human melanocytes in the skin. Such cultures could represent a useful model to study normal behavior and tumor progression of pigmented cells.
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PMID:Expression of cell surface sialic acid and galactose by normal adult human melanocytes in culture. 238 67

Ovarian carcinoma cell clusters were isolated from patient effusions. The cell isolates were incubated in vitro with radioactive glycoconjugate precursors. Radiolabelled glycoconjugates released to culture media were analyzed for molecular mass heterogeneity and lectin binding activity. From 10 to 50% of the released glycoconjugates were present as a heterogeneous array of glycoconjugates of molecular mass greater than 250 kilodaltons. The remaining glycoconjugates were dispersed in a molecular mass range extending down to approximately 15 kilodaltons. Concanavalin A-Sepharose affinity chromatography revealed the presence of N-linked oligosaccharides. Interaction of glycoconjugates with lentil and pea lectins indicated the presence of L-fucose residues linked to asparagine-bound N-acetylglucosamine. Precipitation of glycoconjugates with ricinus communis agglutinin I showed the presence of nonreducing terminal N-acetyllactosamine residues. Collectively, the data indicate that ovarian carcinoma cells release to culture medium fucosylated glycoconjugates bearing complex-type oligosaccharides. The synthesis and release of these glycoconjugates showed no significant differences among different histologic types of ovarian carcinoma; however, modulation as a function of tumor progression may occur.
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PMID:Synthesis and release of glycoconjugates bearing N-linked oligosaccharides by ovarian carcinoma cells isolated from effusions. 273 50

Spontaneous wheat germ agglutinin (WGA)-resistant mutants of the MeWo human malignant melanoma line were isolated after sequential selection in increasingly toxic concentrations of WGA, without prior mutagenesis. They were isolated in an attempt to obtain "membrane glycosylation mutants" having significantly altered metastatic properties when grown in nude mice, and to characterize the biochemical (oligosaccharide) changes associated with altered metastatic behavior. The lines were assessed for their sensitivity to other lectins, membrane glycoprotein profiles, ploidy levels, and their ability to produce "artificial" metastases in nude mice after i.v. inoculation. One mutant, called 70-W, manifested a 3- to 4-fold resistance to WGA compared with wild-type cells. When inoculated into NIH Swiss nude mice, 70-W cells not only produced extensive lung colony formation but also showed an extraordinary ability to disseminate widely and extensively in a clinical fashion to many extrapulmonary sites such as the subcutis, mesentery, muscle, and brain. Moreover the majority of these metastases were deeply pigmented facilitating visual identification of very small visceral metastases. A second mutant called 3S5 was isolated and found to be highly resistant to WGA (greater than 20-fold resistance). This line was virtually devoid of metastatic ability and was found by biochemical analysis to be phenotypically similar to the class I WGA resistant non-metastatic mutants previously isolated from the highly metastatic murine tumor MDAY-D2 which are known to be deficient in sialic acid and galactose. The similarity between these and earlier results using lectin resistant mutant rodent cell lines strongly suggests that sialylated glycoconjugates contribute to the metastasis of both animal and human tumors of different tissue origin. These new spontaneously derived WGA resistant MeWo mutants should be valuable new tools for the study of human tumor progression in vivo and factors involved in metastasis, especially the contribution of oligosaccharide moieties of cell surface glycoconjugates.
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PMID:Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. 333 29

Native natural killer (NK) cells comprise a heterogeneous family of lymphocytes distributed among several organs, which display spontaneous cytotoxic reactions directed against a broad range of tumor targets. In these studies, murine cell lines have been established in vitro following the selective expansion of bone marrow- and spleen-derived killer progenitors in culture medium supplemented with interleukin-2. Several clones of independent origin have been characterized in order to determine the extent of their phenotypic and functional diversity. With few exceptions most of them were found to be highly effective in lysing a variety of tumor cell lines, to share common cell surface alloantigens, lectin-binding receptors, and cytochemical markers. The presence of prominent azurophilic cytoplasmic granules is the most characteristic ultrastructural feature of these cells. In attempting to elucidate the nature of membrane components specifically recognized by NK cells we compared several isogenic tumor cell variants selected on the basis of their differential NK susceptibility, immunogenicity, metastatic potential or resistance to cytotoxic plant lectins. Sialylated glycoconjugates exposed on the external face of the tumor cell membrane appear to be essential determinants in the interaction between NK cells and their targets. Permanent cell lines retaining most of the functional attributes of endogenous NK cells may prove instrumental in understanding their role during tumor progression.
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PMID:Neoplastic cells as targets of spontaneously cytotoxic lymphocytes: studies with natural killer-like cell lines. 638 43

Previous studies demonstrated that growth in DBA/2 mice of MDW4, a wheat germ agglutinin-resistant (WGAr) mutant of the highly metastatic MDAY-D2 DBA/2 mouse tumor, led to the emergence of WGA-sensitive (WGAs) revertants having higher ploidy levels at the site of inoculation as well as at distant visceral metastases. The results implied that MDW4 was nonmetastatic but progressed to become metastatic in vivo only after a cellular change took place which was accompanied by extinction of the WGAr phenotype and acquisition of a higher number of chromosomes. Results presented here provide strong and direct evidence for the underlying mechanism being spontaneous cell fusion in vivo between the MDW4 (WGAr) tumor cells and normal host cells, at least some of which are of bone marrow origin. Thus, growth of the H-2d MDW4 tumor cells in (C3H X DBA/2)F1 (H-2k X H-2d) or (C57BL/6 X DBA/2)F1 (H-2b X H-2d) mice led to the appearance of WGAs revertants bearing the H-2k or H-2b major histocompatibility complex antigens associated with the C3H or C57BL/6 parental strains, respectively. Similarly, WGAs revertants of MDW4 were found to express H-2k antigens after growth in CBA/HT6T6 (H-2k) leads to DBA/2 bone marrow radiation chimeras. Attempts to mimic the in vivo hybridization process were successful in that in vitro somatic cell fusion between an ouabain-resistant (OuaR), 6-thioguanine-resistant (Thgr) derivative of the MDW4 mutant and either normal bone marrow or spleen cells resulted in loss of the WGAr phenotype in the hybrids (thus showing its recessive character) and increased malignant properties in vivo. An analysis of spontaneous frequencies of re-expression of various drug resistance genetic markers in several hybrid metastatic cells was also consistent with chromosome segregation of the sensitive alleles. The results show that tumor progression and the emergence of metastatic cell variants could arise as a consequence of tumor X host cell fusion followed by chromosome segregation. We also discuss the possibility that this type of event may normally be a very rare one during the growth of tumors, the frequency of which can be artificially amplified by the use of certain classes of lectin-resistant mutants carrying particular cell surface alterations.
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PMID:Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor. 668 20


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