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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel model of tumor progression in metastatic cancer is described which grew out of attempts to derive stable non-metastatic variants from a highly metastatic mouse tumor called MDAY-D2. The variants were obtained by selection of so-called lectin-resistant (LecR) membrane mutants using toxic concentrations of wheat germ agglutinin (WGA) as the selective agent, after mutagenesis. Cloned WGAR variants almost all appeared to be highly tumorigenic and metastatic, but displayed altered growth properties which were highly suggestive of major cellular phenotypic alterations occurring prior to metastasis. This were confirmed with the discovery that spontaneous visceral metastases always consisted of WGA-sensitive (WGAS) 'revertant' tumor cells. Such revertants also arose at the site of the subcutaneous inoculation and, with time, comprised an increasing proportion of the tumor cells at that location. The WGAS/high metastatic phenotype was stable in vitro or in vivo, implying the WGAR leads to WGAS shift had an underlying genetic basis. Thus, it appeared that the WGAR tumor cells could not metastasize, because of either an intrinsic cellular defect or a host imposed barrier, but that this block could be circumvented through a genetic change in the WGAR tumor cells which was accompanied by reversion of the WGAR phenotype. Non-tumorigenic (tum-) WGAR variants were also obtained, but in these cases the mutagenesis treatment itself appeared responsible for development of the tum- phenotype. The reduced tumorigenicity had an underlying immunological basis, a finding which could be exploited to immunotherapeutically treat established visceral metastases of poorly immunogenic tumors. Throughout these studies, emphasis was placed on the considerable potential of using tumor cell populations having various stable drug-resistant genetic markers to monitor aspects of tumorigenesis, tumor progression, and metastasis.
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PMID:Tumor progression in metastasis: an experimental approach using lectin resistant tumor variants. 676 77

A positive correlation between tumor progression in human colon and increased beta 1,6 branching in oligosaccharides has recently been demonstrated. The present study was undertaken to elucidate whether such a correlation can be extended to variants of metastasizing human colon carcinoma HCT116 cells. The Phaseolus vulgaris leukoagglutinating lectin, which binds to beta 1,6 branched oligosaccharides, was employed. In blots, a band of approximately 140 kd was detectable in both the HCT116a and HCT116b sublines. However, in the more aggressive subline HCT116a, the intensity of this band was increased by 100%, and additional reactive bands of approximately 100 kd and approximately 170 kd were observed. Analysis by electron microscopy revealed lectin labeling in the Golgi apparatus, lysosomal elements, mucus droplets, cytoplasmic vesicles, and at the plasma membrane. Quantification of the lectin plasma membrane labeling revealed a significantly higher labeling intensity in HCT116a cells than in HCT116b cells. The difference in lectin plasma membrane labeling intensity could also be observed in paraffin sections. Thus, variants of metastatic HCT116 colon carcinoma cells differ quantitatively and qualitatively in glycoproteins carrying beta 1,6 branches.
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PMID:Cytochemical staining for beta 1,6 branching of asparagine-linked oligosaccharides in variants of metastatic human colon carcinoma cells. 751 29

The Mac-2 lectin (carbohydrate binding protein 35) is a soluble, 32- to 35-kDa phosphoprotein that binds galactose-containing glycoconjugates. We report here that the colonic epithelium is a major site of Mac-2 expression in vivo based on immunohistochemistry of human tissue specimens. In this epithelium, proliferating cells at the base of the crypts do not express Mac-2 but its expression increases with differentiation along the crypt-to-surface axis. Mac-2 expression is concentrated in the nuclei of these differentiated epithelial cells. The progression from normal mucosa to adenoma to carcinoma is associated with significant changes in Mac-2 nuclear localization and expression. In all adenomas (9/9) and carcinomas (13/13) examined, Mac-2 was not present in the nucleus but was localized in the cytoplasm. Sequencing of Mac-2 cDNAs from normal mucosa and carcinoma revealed no specific mutations that could account for this loss of nuclear localization. We also observed a 5- to 10-fold decrease in Mac-2 mRNA levels in cancer compared to normal mucosa as well as a significant reduction in the amount of Mac-2 protein expressed. These observations suggest that Mac-2 exclusion from the nucleus and its decreased expression may be related to the neoplastic progression of colon cancer.
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PMID:Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma. 768 4

Human hepatocellular carcinoma (HCC) is characterized by hypervascularity and tumor staining in angiograms, and tumor angiogenesis is considered indispensable for tumor growth. HCC is also characterized by an obvious multistage process of tumor progression. To find out in which stage of human hepatocarcinogenesis angiogenesis occurs, we have carried out a pathological study, of the phenotypic changes in tumor vessels taken from surgically resected liver tumors showing each step of the progression. Eleven early advanced HCCs (advanced HCC component in early HCC nodule, eAd HCC), seven early HCCs (eHCC) and six adenomatous hyperplasias (AH), the non-tumorous liver surrounding each and five normal livers were studied by lectin histochemistry and immunohistochemistry. The sinusoidal endothelial cells from the non-tumorous liver were shown to be negative for UEA-I (Ulex europaeus I), but the endothelial cells from the sinusoidal tumor vessels in advanced HCC components were strongly positive. In AH and eHCC, half the tumors were negative and the other half focally positive. In the early HCC lesion of eAdHCC, the rate of positivity for UEA-I was a little higher than in AH and eHCC but lower than in advanced HCC lesions in eAdHCC. Immunohistochemically, laminin was not detected in the sinusoids in the non-tumorous liver or in the sinusoidal tumor vessels in AH and eHCC. In eAdHCC, however, two early HCC lesions and four advanced HCC lesions were positive. An immunohistochemical examination for muscle actin revealed an increase in arterial tumor vessels in six advanced HCC lesions and one early HCC lesion of eAdHCC. The results indicate the emergence of UEA-I-positive sinusoidal tumor vessels to be most pronounced during the progression from eHCC to advanced HCC, and laminin-positive sinusoidal tumor vessels or actin-positive arterial tumor vessels to emerge mainly in advanced HCC.
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PMID:Phenotype changes in tumor vessels associated with the progression of hepatocellular carcinoma. 768 37

Rat Nb 2 lymphoma cells have been widely used to bioassay human growth hormone and many species of prolactin. Because their morphologic characterization suggests a T-cell lineage, Nb 2 cells were examined for their response to the T-cell mitogens concanavalin A, pokeweed mitogen, and phytohemagglutinin P. As expected, a dose-response to rat prolactin was observed; however, attempts to induce proliferation using the conventional T-cell mitogens failed at concentrations normally stimulatory for rat primary lymphocytes. Moreover, when Nb 2 cells were simultaneously incubated with lectin plus a suboptimal concentration of prolactin, a dose-dependent suppression of the stimulatory effects of prolactin was observed with phytohemagglutinin P and pokeweed mitogen, although not with concanavalin A. Culture medium of prolactin-stimulated Nb 2 cells also contained a factor which inhibited normal rat lymphocyte activation by concanavalin A. The factor did not block induction of the IL-2 receptor and proliferation of IL-2-dependent CTLL-2 cells could be restored by exogenous IL-2. Because Nb 2 cells evolved from a lactogen-dependent lymph node tumor, these results may have implications for further understanding the role of pituitary hormones, particularly prolactin, in the immune response to hormone-dependent tumor progression.
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PMID:Mechanisms of activation and suppression in rat Nb 2 lymphoma cells: a model for interactions between prolactin and the immune system. 779 91

The morphology of the microcirculation of uveal melanomas is a reliable market of tumor progression. Scanning electron microscopy of cast corrosion preparations can generate three-dimensional views of these vascular patterns, but this technique sacrifices the tumor parenchyma. Formalin-fixed wet tissue sections 100-150 microns thick from uveal melanomas were stained with the lectin Ulex europaeus agglutinin I (UEAI) and proliferating cell nuclear antigen (PCNA) to demonstrate simultaneously the tumor blood vessels and proliferating tumor cells. Indocarbocyanine (Cy3) was used as a fluorophore for UEAI and indodicarbocyanine (Cy5) was used for PCNA. Double labeled sections were examined with a laser scanning confocal microscope. Images of both stains were digitized at the same 5-microns intervals and each of the two images per interval was combined digitally to form one image. These combined images were visualized through voxel processing to study the relationship between melanoma cells expressing PCNA and various microcirculatory patterns. This technique produces images comparable to scanning electron microscopy of cast corrosion preparations while permitting simultaneous localization of melanoma cells expressing PCNA. The microcirculatory tree can be viewed from any perspective and the relationship between tumor cells and the tumor blood vessels can be studied concurrently in three dimensions. This technique is an alternative to cast corrosion preparations.
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PMID:Three-dimensional relationships between tumor cells and microcirculation with double cyanine immunolabeling, laser scanning confocal microscopy, and computer-assisted reconstruction: an alternative to cast corrosion preparations. 790 12

The expression of glycoconjugates specific to Jack fruit lectin (JFL) was studied in the exfoliated squamous cells of different grades of intraepithelial and invasive neoplasia of the uterine cervix. It was observed that while normal cells showed almost negative binding, the lectin binding percentage of squamous cells significantly increased with increasing atypia of the epithelium. Correlation analysis between different groups revealed that mild lectin binding in cells had a negative correlation and intense binding had a positive correlation with various stages of tumor progression. These results indicate that the number of cells with aberrant expression of glycoconjugates increases as neoplastic transformation advances. The percentage of labeled and unlabeled cells also shows a continuous transition from low to severe grades of cervical intraepithelial neoplasia and invasive carcinomas. The present study therefore shows that JFL may be used as a probe for further elaboration of detection and grading of precancerous and cancerous lesions of the uterine cervix.
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PMID:Jack fruit lectin-specific glycoconjugate expression during the progression of cervical intraepithelial neoplasia: a study on exfoliated cells. 792 7

Alterations of the N-linked carbohydrate core structure of cell surface glycoproteins (beta 1-6 branching) can be detected by phytohemagglutinin (PHA-L) lectin binding and has been linked to tumor progression and K-ras activation in colon cancer. The purpose of this study was to determine the prevalence of this carbohydrate alteration and its relationship to K-ras activation in pancreatic cancer. Nine human pancreatic cancer cell lines and 4 colon lines as controls were grown under standard tissue culture conditions. K-ras genome analysis was performed by polymerase chain reaction amplification and sequencing. The proportion of cellular p21-ras bound to GTP (ras-GTP level) was determined using immunoprecipitation of 32P-labeled cell lysates followed by thin layer chromatography and phosphoimaging analysis. Lectin blot analysis was performed on crude membrane preparations. Sensitivity to lectins was assessed with cell culture thymidine incorporation. Of 9 pancreatic cancer lines tested, 3 had wild type K-ras, 2 had heterozygous and 4 had homozygous mutations in codon 12 of K-ras. These genotypes correlated strongly with the level of ras-GTP measured. K-ras mutants had increased levels of ras-GTP compared to wild-type cell lines. PHA-L binding to cell membranes correlated positively with ras-GTP levels in 7 out of 9 cell lines. PHA-L toxicity was greatest in cells with positive PHA-L reactivity on Western blotting. A positive correlation between the presence of K-ras mutation, increased ras-GTP level, and increased cell surface beta 1-6 N-linked carbohydrate exists in pancreatic cancer cell lines.
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PMID:Phytohemagglutinin-L (PHA-L) lectin surface binding of N-linked beta 1-6 carbohydrate and its relationship to activated mutant ras in human pancreatic cancer cell lines. 894 26

In human colon carcinoma, increased amounts of sialic acids have been found and correlated with tumor progression. Further, the degree of O-acetylation of sialic acid residues in normal mucosa is higher than in colon carcinoma. Thus, tumor-associated sialylated antigens may be constitutively expressed in O-acetylated form in normal mucosa unreactive with the respective monoclonal antibodies. We have earlier demonstrated a colon carcinoma-associated expression of alpha 2,6-linked sialic acid residues with the Sambucus nigra agglutinin (SNA). We report now that de-acetylation of normal and transitional colonic mucosa, in contrast to sialyl-Tn antigen, does not result in SNA binding. Further, the alpha 2,6-linked sialic acid recognized by SNA is distinct from that of sialyl-Tn antigen. This is confirmed by Northern blotting detecting transcripts for alpha 2,6 sialyltransferase of N-glycoproteins and measurement of activity for this sialyltransferase. Blot analysis by SNA of colon carcinoma cells revealed few reactive glycoproteins. Quantitative differences in lectin labeling and sialyltransferase activity were found in HCT116 colon carcinoma cell sub-lines. Our data suggest that SNA binding in human colon carcinoma is due to de novo expression of a specific sialic acid present on selected glycoproteins.
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PMID:Colon carcinoma glycoproteins carrying alpha 2,6-linked sialic acid reactive with Sambucus nigra agglutinin are not constitutively expressed in normal human colon mucosa and are distinct from sialyl-Tn antigen. 905 58

In this report we describe the characteristics of an immunosuppressive molecule from an Abelson Leukemia Virus transformed highly malignant and metastatic RAW117-H10 murine large cell lymphoma cells. Our studies have shown that the mitomycin-c treated or irradiated RAW117-H10 cells very significantly (p < 0.001) inhibited the nitrogen induced proliferation of normal Balb/c splenocytes. The cell surface extracts from the immunosuppressive RAW117-H10 lymphoma cells significantly inhibited the in vitro T cell or NK/LAK cell functions. Our in vivo studies demonstrated that there was a significant suppression of immune response in the Balb/c mice bearing RAW117-H10 cells when compared with mice bearing low metastatic parental RAW117-P cells or control mice. Subsequently we isolated and purified the main molecule responsible for this immunosuppression and found that the molecule is a glycoprotein with a molecular weight of 70 kD with an isoelectric point of 4.3, which cross reacted with antibodies to murine leukemia virus envelope gp70 molecules. Further analysis using immunoelectrophoresis, molecular probing techniques, and mannose specific lectin binding assay revealed that the immunosuppressive 70 kD molecule, is different from the wild type MLV envelope gp70 molecule and thus appears to be an altered gp70 molecule. These studies demonstrate that the metastatic lymphoma associated immunosuppression may facilitate the growth and metastasis of tumor cells. Our results also elucidate the possible mechanism(s) of retrovirus induced immunosuppression and the molecular basis of this retroviral envelope-mediated process in viral pathogenesis and tumor progression.
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PMID:Immunosuppression by metastatic lymphoma derived altered retroviral gp70 molecule. 920 41


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