Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

A panel of fluorescein-conjugated lectins was used to investigate the cell surface carbohydrates of cell lines isolated from a mouse mammary adenocarcinoma which differ markedly in their morphological and metastatic properties. The lectin-binding profiles of the cells showed them to express generally similar cell surface characteristics; however, two minor differences were evident. Galactose moieties recognized by peanut lectin were expressed on all highly metastatic fusiform cell types examined, but only on 50-60 per cent of the polygonal cells of limited metastatic capacity. Similarly, N-acetylgalactosamine moieties were demonstrated on fusiform cell types by soya bean lectin binding but were not expressed on intact polygonal cells. In both cases pretreatment of polygonal cells with neuraminidase allowed lectin binding comparable with that of fusiform cells suggesting that Gal and GalNAc sugars were abundantly present but masked by sialic acid residues. Using a novel technique in which tumour cells were incubated on cryostat sections of normal tissues, it was found that the cell lines exhibited different adhesion patterns which to some extent reflected their preferential sites for spontaneous metastasis and organ colonization in vivo. Thus the adherence of fusiform cells to liver was five times as great as that of polygonal cells, whereas the latter bound preferentially to lung tissue. Prior treatment of polygonal cells with neuraminidase doubled their frequency of attachment to liver sections, but had no effect on their binding to other tissues. Also, the presence of 100 mM N-acetylgalactosamine during incubation specifically inhibited the adherence of fusiform cells to liver tissues, but did not significantly influence other cell-tissue interactions. The data suggest that the expression of galactosyl or N-acetylated galactosyl groups on the fusiform cells facilitates their attachment to lectin-like receptors on liver cells and contributes to their superior capacity, compared with polygonal cells, for growth and metastasis in this organ.
Clin Exp Metastasis
PMID:Studies of mammary carcinoma metastasis in a mouse model system. II: Lectin binding properties of cells in relation to the incidence and organ distribution of metastases. 654 7

The levels of UDP-galactose: N-acetylglucosamine(beta 1-4)galactosyltransferase activity (GalT-4) were determined in the sera, in solid tumors, and in corresponding cell cultures of rats bearing two lines of prostate adenocarcinomas (PA-2 and PA-3), and in the sera of rats bearing other transplanted and autochthonous adenocarcinomas. Sera and tissues from normal (tumor-free) rats were used as controls. Prostate adenocarcinoma cell cultures had five times greater levels of enzyme activity than did tumor cell infiltrated lymph nodes from animals bearing the prostate adenocarcinomas. The levels of activity in the cells of both prostate tumor lines were equivalent, even though they metastasize through different routes. Serum levels of galactosyltransferase activity were detected in the blood, and in rats bearing a mammary adenocarcinoma with extensive necrosis of the tumor mass (tumor mass greater than 22.0 g/200 g body weight). The increase was three times the control value. The sera of L-W rats bearing prostate tumors (PA-2 and PA-3) were inactive with the GalNAc-containing acceptor, Gm2 (GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4Glc-Cer) but active with either free GlcNAc (Km = 0.25 mM) or LcOse3Cer (GlcNAc beta 1-3 Gal beta 1-4Glc--Cer; GlcNAc--R).
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PMID:Increased activity of a beta-galactosyltransferase in tissues of rats bearing prostate and mammary adenocarcinomas. 680 31

Altered expression of ABH blood group substances is a common feature of human colorectal carcinoma, yet it remains unclear how these structural changes influence the biological properties of tumor cells. Azoxymethane-induced rat colon tumors display many features of the human disease, thereby providing a potentially useful model to study the role of blood group substances in colon cancer progression. We have prepared monoclonal antibodies to a microsomal fraction isolated from an azoxymethane-induced rat colon tumor and selected an antibody that detects cancer-associated changes. Monoclonal antibody (mAb) 3A7 recognizes a determinant on type 2 chain blood group A (GalNAc alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) and B (Gal alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) oligosaccharides. Expression of the epitope detected by this antibody was developmentally regulated in rat colon, with maximal expression from day 4-21 after birth. Immunohistochemical staining and Western blotting analyses of azoxymethane-induced colon tumors revealed increased expression of the epitope in all of the 21 colonic tumors examined, including preneoplastic glands within transitional mucosa. Conventional and signet-ring adenocarcinomas that had invaded through the muscularis propria (Duke's B2) consistently showed the most intense staining with mAb 3A7, including regions depicting angioinvasion. Some of the lymph node metastases (Duke's C2) stained poorly with the antibody. The epitope was also expressed in blood group A positive human colon carcinoma cell lines, including HT29 and SW480 but not by SW620, a cell line derived from a lymph node metastasis isolated in vivo from the SW480 primary tumor, or in the blood group B cell line SW1417. The glycoproteins detected by mAb 3A7 in rat colon tumors and HT29 cells ranged in size between 50 and 200 kd, including a major species of 140 kd. Affinity chromatography of detergent lysates of normal rat colon on the blood group A specific lectin Dolichos biflorus (DBA)-agarose resulted in nearly quantitative binding of glycoprotein species detected by the antibody. By contrast, immunoreactive glycoproteins from rat colon tumors or HT29 cells bound poorly to DBA-agarose but were retained by another blood group A-binding lectin, Helix-pomatia (HPA)-agarose. These results indicate that colon carcinogenesis results in quantitative as well as qualitative changes in oligosaccharides detected by mAb 3A7 and suggest that the combined use of mAb 3A7 and blood group A-specific lectins may provide a useful tool for early detection of colon cancer.
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PMID:Monoclonal antibody recognizing a determinant on type 2 chain blood group A and B oligosaccharides detects oncodevelopmental changes in azoxymethane-induced rat colon tumors and human colon cancer cell lines. 753 50

The extent of lectin binding by three human melanoma (LOX, FEMX-1 and SESX) and two sarcoma lines (MHMX and OHSX) was related to their potential for experimental metastasis formation in athymic nude mice. The Helix pomatia agglutinin (HPA), which recognises the N-acetyl-D-galactosamine ligand, showed differential binding to the cell lines in a manner that correlated with their ability to give lung colonies after i.v. injection in the mice (P < 0.005). The degree of HPA binding and lung colony formation of the cell lines studied was ranked in the following order, LOX > MHMX > OHSX > SESX > FEMX-I. Similar patterns were not observed with the other lectins used in this study (WGA, Con A, PNA and UEA-I). The high HPA reacting LOX melanoma line shows extensive pulmonary metastatic formation with no extrapulmonary colonies, whereas the low HPA reacting FEMX-I cells give only extrapulmonary metastases with no detectable colonies in the lungs. Precoating of tumour cells with HPA prior to injection did not reduce the ability of cells to give pulmonary metastases, suggesting that the HPA epitope was not functionally associated with the pulmonary metastatic potential observed in nude mice. These findings support recent human studies of a correlation between HPA binding and incidence of metastasis, however, our data indicate that there is no causal relationship. Further analyses are required to identify the specific HPA-binding glycoconjugates that may be involved.
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PMID:Helix pomatia agglutinin binding in human tumour cell lines: correlation with pulmonary metastases in nude mice. 819 63

Frozen sections of primary and metastatic human renal cell carcinoma (RCC) were analyzed for the expression of endogenous binding sites for carbohydrates. Fluorescent neoglycoproteins, carrying chemically linked carbohydrate residues on bovine serum albumin as a carrier protein, were applied to 44 primary tumor specimens. In the majority of specimens, accessible binding sites with specificity for maltose and N-acetylgalactosamine were detected. In specimens of normal kidney no specific binding of carbohydrate ligands was observed under these experimental conditions. Specimens of both the primary tumor and a metastasis were available in 10 cases. When the expression of specific binding sites of primary tumors and metastases was compared, the respective patterns were similar with no clear gain or loss of certain lectins in the metastases. We conclude that binding sites with specificity for maltose and N-acetylgalactosamine are present on human RCC and their corresponding metastases.
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PMID:Detection of endogenous receptors for carbohydrate ligands in primary and metastatic human renal cell carcinoma. 821 20

We have previously identified a neutral glycolipid antigen which appears to be a surface antigenic marker for the metastatic subpopulation in the R3230AC rat mammary adenocarcinoma (S.A. Carlsen, M. Barry, and K. Newton, Clin. Exp. Metastasis, 8: 141-151, 1990). In this article we describe the structural characterization of this glycolipid antigen. The sequence of the sugars in the saccharide portion of the molecule was determined by specific glycosidase cleavage and further confirmed by mass spectroscopic analysis. The nature of the linkages between the monosaccharide units was determined by methylation analysis. The final structure was confirmed by NMR analysis and found to be isoglobotetraosylceramide (GalNAc beta 1-3Gal alpha 1-3Gal beta 1-4Gle beta 1-O-ceramide). We also present evidence that the cells marked by this antigen have a higher metastatic potential than the cells lacking this glycolipid as measured by the formation of lung colonies after i.v. injection of the cells into the tail vein of the rat. Furthermore, isoglobotetraosylceramide seems to play a direct role in the metastatic process since the blocking of exposed antigen with monoclonal antibodies, or their Fab fragments, results in a highly significant decrease in lung colony formation.
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PMID:Isoglobotetraosylceramide is a marker for highly metastatic cells in rat mammary adenocarcinomas. 850 31

Glycoconjugates on the tumour cell surface are functionally important for the interaction of the tumour cell with its environment. Several studies have demonstrated that particular carbohydrate residues on primary cancers are associated with metastasis. Identification of such residues is possible using lectins, including Helix pomatia agglutinin (HPA) which has a nominal monosaccharide specificity for N-acetyl galactosamine (GalNAc) and Phaseolus vulgaris leucoagglutinin (PHA-L) which recognizes beta1-6 branched oligosaccharides. Both lectins have been reported to be valuable prognostic markers in breast and colon cancers. In the present study, the binding patterns of both lectins were investigated on serial sections of human breast cancers and on metastatic and non-metastatic human breast and colon cancer cell lines grown in severe combined immunodeficient (SCID) mice. The two lectins gave very different staining patterns and HPA was more often associated with metastases than PHA-L. Our results indicate that both lectins are not simply recognizing different oligosaccharides associated with the same common metastasis-related glycoconjugate.
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PMID:Do HPA and PHA-L have the same binding pattern in metastasizing human breast and colon cancers? 946 Oct 27

In an experimental model, human melanoma cell lines enriched for cells that express the glycoconjugate B-D galactose N-acetyl-D-galactosamine, which reacts with the peanut agglutinin lectin (PNA), are associated with an increase in the frequency of metastases. We previously showed that this glycoconjugate is expressed on the cells of some primary melanomas in humans and that such cells are found selectively in melanomas with a high risk for developing metastases and causing death. Using fixed archival tissues from 99 primary melanomas and lectin histochemistry, we found 65 tumors that contained melanoma cells that were PNA-positive. PNA-reactive cells were not identified in normal melanocytes or in the nevocytes of 24 nevi. PNA-reactive material accumulates adjacent to the nucleus in the area of the Golgi apparatus, initially as a tiny dot, but later in quantities sufficient to displace and indent the nucleus, producing a signet ring cell-like appearance. Tumor cells containing PNA-reactive material were associated with more evolved, deeper, and thicker tumors. Two melanomas up to Clark level II were PNA positive (20%), compared with 60% of level III, 76% of level IV, and 100% of level V. Five of 13 tumors less than 0.76 mm thick (39%) were positive, compared with 50% of tumors 0.76 to 1.49 mm thick, 64% of tumors 1.5 to 2.99 mm thick, and 85% of tumors 3 mm thick or thicker. PNA-reactivity was negatively correlated with disease-free survival (PNA-negative, 49.2+/-23 months; PNA-positive grade 1, 41.6+/-26 months and PNA-positive grade 2, 24.4+/-23 months), survival rate 5 years after initial treatment (PNA-negative, 84.8%; PNA-positive grade 1, 63.8%; and PNA-positive grade 2, 31.3%) and disease-free survival at 5 years after initial treatment (PNA-negative, 69.7%; PNA-positive grade 1, 53.2%; and PNA-positive grade 2, 25%).
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PMID:Cytoplasmic accumulation of peanut agglutinin-binding glycoconjugates in the cells of primary melanoma correlates with clinical outcome. 1033 27

The expression of carbohydrate antigens has been shown by retrospective immunohistochemical analysis to correlate to the progression and metastases of human cancers. However, the mechanisms of these changes of carbohydrate expression and the role of carbohydrates in the malignant behavior of tumor cells are not well known. In this article, we introduce methods to experimentally modify carbohydrate expression in tumor cells and to assess the involvement of these carbohydrate antigens in the malignant behavior of tumor cells. Modifications of the biosynthesis of O- and N-linked carbohydrates, and glycolipids are achieved by treating cultured tumor cells with culture media containing Benzyl-alpha-GalNAc, swainsonine, or D-PDMP, respectively. Enzymatic digestion of cell surface carbohydrates with sialidase, endo-beta-galactosidase or other glycosidases can also be performed. These cells can be used for short term experiments such as adhesion assays. However, modified carbohydrates may be recovered during in vitro and in vivo assays. By transfection of glycosyltransferase cDNA, or selection of tumor cells by binding lectins or antibodies, stable carbohydrate variant cells can be obtained which are suitable for long term experiments such as the experimental formation of metastases in vivo. The biological function of tumor cell surface carbohydrates may be diverse. These molecules are thought to influence adhesion interaction between tumor cells and the endothelial cells of target organs. However, carbohydrate recognition molecules, or lectins, are expressed on a variety of cells in the vascular system and in the immune system. Therefore, it is essential to design appropriate experimental models to study the biological significance of carbohydrate-lectin interactions in cancer progression and metastatic dissemination. Adhesion assays of tumor cells to selectin-transfected CHO cells were performed. Taking molecules other than selectins into consideration, adhesion assays using frozen tissue sections were also performed.
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PMID:[Tumor metastases and adhesion molecules carbohydrates and lectins]. 1041 Jan 58

This study examines the Helix pomatia lectin (HPA) binding characteristics of metastases arising from primary breast cancer, and compares HPA binding patterns with binding of Dolichos biflorus lectin (DBA), Limax flavus lectin (LFA), and a monoclonal antibody against the Tn epitope. Of 81 blocks of metastases in a range of tissues, taken at autopsy from 46 individuals, 79% were HPA positive. No site specificity with regard to HPA binding was observed. Both HPA-positive and -negative tumour deposits were seen within a single individual. HPA-positive tumours were commonly negative for binding of sialic acid specific lectin LFA (86% were negative). Binding patterns of alpha-GalNAc specific HPA and DBA, and a monoclonal antibody against Tn epitope (GalNAc-O-Ser/Thr) were markedly different.
Invasion Metastasis
PMID:Expression of N-acetyl galactosaminylated and sialylated glycans by metastases arising from primary breast cancer. 1047 24


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