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)

Expression of binding sites for fucose binding proteins (FBP) of Lotus tetragonolobus were immunohistochemically analyzed in surgically extirpated specimens from patients with transitional cell carcinoma of the bladder. The degree of expression of FBP binding sites in the primary cancerous region correlated with the occurrence of lymph node metastasis. Thus, lymph node metastases occurred in 15 of 34 cases with high expression of FBP binding sites, but did not in 17 cases with low or no FBP binding site expression. All metastatic lymph nodes strongly reacted with FBP. In addition, primary lesions at the pT3b or pT4 stage more frequently reacted with FBP as compared with those at the pTa, pT1 or pT2 stage. Although FBP is known to react both with Gal beta 1----4(Fuc alpha 1----3)GlcNAc and Fuc alpha 1----2Gal sequences, comparative staining of other carbohydrate markers revealed that the latter structure is not related with metastatic potential and stages.
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PMID:Reactivity to fucose-binding proteins of Lotus tetragonolobus correlates with metastatic phenotype of transitional cell carcinoma of the bladder. 135 Jun 44

Recently, the ganglioside FucGM1 (Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4[NeuAc alpha 2-3]-Gal beta 1-4Glc beta 1-1 Cer) was identified as a small cell lung cancer (SCLC) marker both in chemical and histochemical studies. In order to further determine whether the FucGM1 ganglioside is shed from the tumor site and consequently is present in the serum of SCLC patients, we produced a series of new monoclonal antibodies raised against FucGM1 and related glycolipids. Shedding of the FucGM1 ganglioside was studied both in vitro and in vivo using SCLC cell lines and nude mice xenografts of SCLC cells as model systems, and finally immunochemical analyses were performed on serum samples from patients with SCLC. High-performance thin-layer chromatography immunostaining demonstrated the presence of FucGM1 in conditioned culture media obtained from FucGM1-positive SCLC cell lines. Furthermore, tumor extracts of SCLC cell line xenografts in nude mice were positive for the FucGM1 marker, and more importantly the marker was also present in serum samples from these mice. Twenty serum samples were obtained from patients with histologically verified SCLC. Eight patients had localized disease, and the remaining patients had disseminated cancer involving metastases to other organ sites. Sera from 4 of these patients were clearly positive, and 2 additional cases were found to be weakly positive. The positive patient sera were all from patients with extensive disease. Sera from 12 patients with non-SCLC and 20 healthy individuals were all found to be negative. These results clearly establish the FucGM1 glycolipid as a potential serum marker of SCLC for which a sensitive immunoassay should be developed and tested using a larger series of serum samples.
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PMID:Immunochemical detection of a small cell lung cancer-associated ganglioside (FucGM1) antigen in serum. 185 63

We observed that two rat colon adenocarcinoma variants originating from a single parental cell line and differing by their progressive and metastatic capacities in syngeneic BDIX rats differed by their organ distribution after intravenous injections. The PROb cells accumulated in the lung, wherefrom the REGb cells were rapidly cleared. In order to explore the role of cell surface glycoconjugates in organ-specific metastasis, cytofluorometric and histochemical studies using labelled lectins were performed. This revealed that the metastatic variant PROb presented more alpha-L-Fuc(1----2) beta D-Gal-R structures than the regressive nonmetastatic variant REGb. At variance, REGb cells exposed more D-galactosyl and N-acetyl-D-galactosaminyl residues than PROb cells. Monosacharides inhibited specifically cell adhesions on frozen organ sections. L-Fuc and N-acetyl-D-galactosamine (D-GalNAc) most strongly inhibited the adhesion of PROb cells on lungs, whereas D-Gal and D-GalNAc most strongly inhibited that of REGb cells. On the liver, adhesions of both cell lines were inhibited by D-Gal and D-GalNAc. These observations support the involvement of sugar-lectin receptors in the adhesion of these cells to the lungs or liver. The possible involvement of previously described lectins is discussed.
Invasion Metastasis 1990
PMID:Correlation between cell surface oligosaccharides and tissue target-selective adhesion of two rat adenocarcinoma cell lines. 226 87

Neoplastic transformation has been associated with a variety of structural changes, among which are changes in membrane carbohydrates. Not much is known, though, e.g., how early in the tumourogenic event these changes take place and what effect these changes have on cell growth, invasion, and ability to metastasize. We were able to identify the B-D-Gal(1-3)DGal-NAc as a membrane carbohydrate component present in malignant laryngeal tissue, but not on adjacent normal mucous membrane. This carbohydrate structure was found to be present in metastatic as well as in nonmetastatic tumours. It was also found in well-differentiated as well as poorly differentiated carcinomas. We suggest that changes in carbohydrate components on the cell membrane of the laryngeal cancer cell are an early event in tumour progression and probably are not related to the degree of invasion or the ability to metastasize.
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PMID:A study of cell membrane structure. 231 4

The lung colonization of MO4 cells, a highly malignant murine cell line, is strongly reduced in syngeneic C3H/He mice by a prior incubation with anti-alpha-galactosyl antibody (alpha-Gal Ab), a natural IgG antibody present in high titers in all normal human sera and specifically recognizing Gal alpha(1----3) structures (alpha-D-galactopyranosyl; alpha-D-Galp). The protective effect is due to a binding of alpha-Gal Ab to alpha-D-Galp end groups of MO4 cells, inducing both an increase in their sequestration into the liver and the spleen and a decrease in their sequestration into the lung. The F(ab')2 fragments of this antibody also exhibit a protective effect by inhibiting the homing of MO4 cells into the lung, without modifying their accumulation into the spleen and the liver. Since both the antibody and the alpha-galactosidase pretreatments of MO4 cells block their subsequent attachment to murine laminin in vitro, we suggest that, in this model, the lung colonization may be dependent on the alpha-D-Galp end groups exposed on the surface of MO4 cells.
Invasion Metastasis 1987
PMID:Human anti-alpha-galactosyl IgG reduces the lung colonization by murine MO4 cells. 332 49

Blood group-related oligosaccharides have been isolated from a limited number of carcinomas. The carcinoma-associated oligosaccharides show chain elongation, for example due to repeating Gal 1,4 GlcNAc 1,3 sequences, or a higher degree of branching, which permit increased sialylation and fucosylation. Abnormal carbohydrate structures have been demonstrated on tumor cell membranes by immunological techniques, which suggests deletion of ABH, accumulation of 'crypt' antigens such as I and T antigens, and abnormal expression of Lewis antigens. Changes in carcinoma-associated oligosaccharides can result from altered biosynthetic processing in the Golgi apparatus or the occurrence of abnormal tumor glycosyltransferase isoenzymes. Structural alterations of oligosaccharides on the tumor cell membrane are related to the regulation of tumor growth, cell-cell interaction, cell differentiation, and metastasis. Glycoproteins secreted by tumor cells into the circulation evoke cellular and humoral immunity and cause immune suppression by binding to cytotoxic T lymphocytes and lymphocyte subsets. The relationship of oligosaccharide structures to biologic function awaits elucidation.
Cancer Metastasis Rev 1987
PMID:The structural relationship of blood group-related oligosaccharides in human carcinoma to biological function: a perspective. 332 32

Numerous investigations suggest that cell surface glycoconjugates, and in particular sialic acids, are directly involved in determining the metastatic phenotype. To further evaluate this hypothesis, we have used a variety of techniques to probe the cell surfaces of several metastatic variants of the murine B16 melanoma that were selected for experimental lung-colonizing ability (Fidler, I. (1973) Nature 242, 148-149) or for their ability to spontaneously metastasize from the site of a subcutaneous injection (Stackpole, C. W., Alterman, A. L., and Fornabaio, D. M. (1985) Invasion & Metastasis 5, 125-142). Using a highly sensitive high performance liquid chromatography sialic acid assay in conjunction with Vibrio cholerae sialidase, we find that none of these metastatic variants differ significantly in their overall levels of cell surface sialic acid. Using highly purified, linkage-specific sialyltransferases, in conjunction with specific glycosidases, to probe the cell surface saccharide topography of specific penultimate oligosaccharides, we also find no significant differences between the efficient lung-colonizing variant, B16-F10 and the poorly-colonizing B16-F1 or B16-Flr variants. In contrast, the spontaneously metastatic variants examined contain substantially different levels of specific penultimate sialylation sites. The tumorigenic but nonmetastatic B16-LM3/G3.26 variant contains 4-fold more penultimate Gal beta 1-3GalNAc sialylation sites than the tumorigenic and highly metastatic B16-LM3/G3.12 variant when CMP[3H]NeuAc and the alpha 2-3Gal beta 1-3GalNAc sialyltransferase are used to probe the melanoma cell surfaces. Several prominent glycoconjugates of apparent Mr 43,000, 40,000, and 30,000 are especially evident upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the nonmetastatic cells. The nonmetastatic variant also contains 2-fold more Gal beta 1-4GlcNAc sialylation sites than the metastatic variant when the alpha 2-6Gal beta 1-4GlcNAc sialyltransferase is used as a cell surface probe. In this case, glycoconjugates of apparent Mr 74,000, 45,000, and 43,000 are more prominently observed on the cell surfaces of the nonmetastatic variant. These data indicate that the differences in lung-colonizing abilities of B16 melanoma metastatic variants do not correlate with the numbers or sialylation states of specific penultimate oligosaccharide structures on their surfaces. However, the relative levels of specific penultimate saccharide structures do correlate with the ability of the cells to undergo spontaneous metastasis from a subcutaneous tumor.
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PMID:Cell surface sialylation and tumor metastasis. Metastatic potential of B16 melanoma variants correlates with their relative numbers of specific penultimate oligosaccharide structures. 337 1

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


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