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

Reliable discriminatory tests to predict metastatic disease would clearly facilitate the management of cancer in the elderly. We have recently identified a 90-110-kilodalton (kDa) cell surface glycoprotein that is differentially expressed in benign and malignant murine adrenal carcinoma cells. In view of the proteins highly glycosylated nature, we have tested its ability to bind to a panel of agarose-bound lectins. Wheat germ agglutinin (WGA), a lectin specific for terminal sialic acid and N-acetylglucosamine (G1cNAc), had a strong affinity for the metastasis-related protein but failed to detect such a glycoprotein in nonmetastatic cells. Treatment of cells with sialidase to remove terminal sialic acids did not affect the affinity of the protein for the lectin, indicating the presence of terminal G1cNAc. We show by in situ that this metastatic binding protein (MBP) is regionally concentrated on the surface of invasive cells but absent in cells unable to invade. We postulate that MBP plays an active role in cell migration through interactions with beta-1,4 galactosytransferase and basement membrane glycoproteines.
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PMID:A murine model for evaluating metastatic potential: characterization of a 90-110-kDa metastasis-binding protein. 142 83

N-Linked sugar chains of normal mammary gland, mammary carcinomas (primary lesion), and axillary lymph node metastases of mammary carcinomas were released from their membrane preparations by hydrazinolysis and their structures were analyzed. Fractionation using a Datura stramonium agglutinin (DSA)-Sepharose column revealed that the metastasized carcinomas contain more than twice as much DSA-binding oligosaccharides as the normal gland, and the primary carcinomas contain an intermediate amount. These oligosaccharides were elucidated to have tri- and tetraantennary structures containing the GlcNAc beta 1-->6(GlcNAc beta 1-->2)Man group with and without N-acetyllactosamine repeating units. Lectin blot analysis of membrane glycoproteins and histochemical staining of tissues using biotinylated DSA indicated that these glycosylation changes predominantly occur in a limited number of glycoproteins with apparent molecular weights of 90, 160, and 210 kilodaltons, and mammary carcinomas are distinguishable from normal gland by their intense intracytoplasmic staining.
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PMID:Altered glycosylation of membrane glycoproteins associated with human mammary carcinoma. 145 59

Immunochemical studies of human colorectal carcinoma with various monoclonal antibodies against Le(X)-related carbohydrate antigens previously revealed that the amount of sialyl-dimeric Le(X) antigen (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-R: SLX) associated with metastatic lesions was greater than in the primary tumors. To assess whether an experimental model can be used to study the direct relationship between this carbohydrate antigen and the tumor cell's metastatic behavior, we selected variant cells with increased surface SLX from established human colon carcinoma cell line HT-29. The cells in the upper 5% or lower 5% population in fluorescence intensity after reacting with a monoclonal antibody, FH6, were retrieved separately by a fluorescence-activated cell sorter and propagated. After three- or four-times selection, we obtained stable cell lines with low and high cell surface SLX antigens (HT-29 M1 and HT-29 M2, respectively). Binding of monoclonal antibody FH6 was detected to glycolipids extracted from HT-29 M2 cells but not from HT-29 M1 cells. Glycoprotein components having reactivity with monoclonal antibody FH6 were below the detectable level. HT-29 M2 cells injected intrasplenically into nude mice showed a slightly reduced incidence of metastasis to lung, liver and lymph nodes than did HT-29 M1 cells. Subsequently we found that SLX antigen was not detectable by immunohistochemical examination of these tumor cells grown in nude mice. Re-established cell line from nude mice xenografts expressed SLX antigen in vitro.
Clin Exp Metastasis
PMID:Metastatic behavior and cell surface properties of HT-29 human colon carcinoma variant cells selected for their differential expression of sialyl-dimeric Le(x)-antigen. 167 54

We have examined the binding and functional activity of monoclonal antibody (MAb) SG-1 that was raised by immunization against embryonal carcinoma cells and screened using KHT fibrosarcoma cells. Quantitative absorption, binding and in situ immunochemical staining assays indicate that the MAb SG-1-defined epitopes are expressed preferentially by the highly metastatic KHT35-L1 cells relative to the weakly metastatic, parental KHTp cells. Furthermore, there was a significant correlation (p less than 0.05) between the expression of MAb SG-1-defined antigen on the cells, following trypsin treatment, and their metastatic ability. Binding of MAb SG-1 to antigen was inhibited by specific sulfated polysaccharides including cerebroside sulfate (brain sulfatide), fucoidan, and dextran sulfate (500 kD) but not by heparan, chondroitin, keratan or dextran (5 kD) sulfates. Initial characterization of antigen from KHT cells indicates that the epitope of MAb SG-1 is defined by sulfated glycoconjugates containing galactose and sulfate but not N-acetylglucosamine. In the total lipid extracts of KHT35-L1 cells the antigen was detected in the delipidated protein fraction as well as in the chloroform/methanol fraction. These results suggest that the sulfated glycoconjugate determinants identified by MAb SG-1 may be relevant to the metastatic process of KHT fibrosarcoma cells.
Clin Exp Metastasis
PMID:Sulfated glycoconjugate determinants recognized by monoclonal antibody, SG-1, correlate with the experimental metastatic ability of KHT fibrosarcoma cells. 169 55

Malignant transformation of murine and human cells is commonly associated with increased--GlcNAc beta 1-6Man alpha 1-6Man beta--branching in asparagine-linked oligosaccharides. Somatic mutations and drugs which block expression of the beta 1-6 branched oligosaccharides are potent inhibitors of tumor cell invasion and metastasis in animal models. This suggests that the oligosaccharides are required for metastasis to occur and therefore their increased presence in primary tumors may be diagnostic of metastatic disease. Although antibodies to the beta 1-6 branched portion of the oligosaccharides are not available, a plant lectin leukoagglutinin (L-PHA) has been shown to bind specifically to this structure. L-PHA lectin histochemistry was performed on paraffin sections of human breast and colon tissues. All breast carcinomas and epithelial hyperplasia with atypia showed significantly increased L-PHA staining compared to fibroadenomas and hyperplasia without atypia. In histological sections of colon, adenomas showed a small but significant increase in L-PHA staining compared to normal colonic epithelium, while carcinomas showed greatly increased reactivity. In addition, Dukes stage C tumors showed higher levels of L-PHA staining than stage A tumors. These results demonstrate that L-PHA-reactive beta 1-6 branched N-linked oligosaccharides are consistently increased in neoplasias of human breast and colon and that the level of L-PHA staining correlates with the pathological staging of the diseases.
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PMID:Beta 1-6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia. 826 56

Trophoblast cells of normal first trimester human placenta share with malignant tumor cells the ability for significant cellular proliferation and invasion of basement membranes. Because tumor cell metastasis in vivo and invasion of basement membranes in vitro have recently been shown to require the expression of -GlcNAc beta 1-6 Man alpha 1-6 Man beta 1-branched complex type Asn-linked oligosaccharides in tumor cell surface glycoproteins, we decided to determine if such structures were also necessary for invasion by trophoblast cells. We report here that invasive first trimester trophoblasts express leukoagglutinin-reactive beta 1-6 branched Asn-linked oligosaccharides on their surface. Moreover, basement membrane invasion by trophoblast was significantly inhibited by pretreating the cells with swainsonine, a non-toxic inhibitor of Golgi alpha-mannosidase II which blocks beta 1-6 branching of Asn-linked oligosaccharides. The first trimester trophoblast cells pretreated with swainsonine attached more avidly to the amnion basement membrane and to an extracellular matrix (ECM) preparation compared to control non-treated erophoblast cells. Swainsonine treatment did not inhibit secretion of gelatinase or plasminogen activator activities by trophoblast cells. These results suggest that expression of beta 1-6 branched oligosaccharides in trophoblast cells may be functionally important for the implantation and placentation processes by reducing cell adhesion to ECM and thereby facilitating trophoblast cell invasion.
Clin Exp Metastasis
PMID:Basement membrane invasion by first trimester human trophoblast: requirement for branched complex-type Asn-linked oligosaccharides. 211 36

Assessment is made of the presence or absence of specific sugar receptors (lectins) in patients operated for intrapulmonary metastases of osteogenic sarcoma. Investigations were carried out on histochemically stained paraffin sections for the separate types of sugars. Highest was the presence of specific receptors for sialic acid and for N-acetylglucosamine, followed by those for ramnose and heparin and least for mannose and maltose. Lectin determination is a new branch in morphological science, assisting clinical practice, special surgical activity by the attempt for quantitative grading of cell populations in norm and in their neoplastic development.
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PMID:[An evaluation of endogenous lectins in the intrapulmonary metastases of osteogenic sarcoma]. 239 6

In previous studies we have shown that the ability of murine tumor cells to metastasize in situ is directly linked to expression of -GlcNAc beta 1-6Man alpha 1-6Man beta 1-branched complex-type Asn-linked oligosaccharides in tumor-cell glycoproteins. Here we demonstrate that cell-surface expression of beta 1-6 branched oligosaccharides in metastatic tumor cells is specifically associated with increased invasion of human amnion basement membranes in vitro. Compared to nonmetastatic SP1 murine mammary carcinoma cells, 2 metastatic sublines expressed higher levels of beta 1-6 branched oligosaccharides and were found to be invasive but poorly adhesive on the amnion basement membrane. Swainsonine, a non-toxic inhibitor of Asn-linked oligosaccharide processing which blocks the pathway prior to initiation of the beta 1-6 linked antenna, blocked metastatic tumor-cell invasion and increased adhesiveness. Swainsonine and the metalloprotease inhibitor O-phenanthroline inhibited invasion, apparently via independent mechanisms. O-phenanthroline did not affect tumor-cell adhesion to the amnion basement membrane and swainsonine did not block secretion of metalloproteases, beta-hexosaminadase or tissue plasminogen activator activity by the tumor cells. These results suggest that tumor-cell invasion of basement membranes requires both secretion of hydrolase activities and expression of beta 1-6 branched complex-type oligosaccharides at the tumor cell surface, such oligosaccharides being associated with reduced tumor-cell adhesion to extracellular matrix.
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PMID:Evidence that beta 1-6 branched Asn-linked oligosaccharides on metastatic tumor cells facilitate invasion of basement membranes. 250 55

Increased--GlcNAc beta 1-6Man alpha 1-6Man beta--branching in asparagine-linked oligosaccharides has been observed in murine and human tumor cells and has recently been linked to enhanced metastatic potential in experimental tumor models. Leukoagglutinin (L-PHA) requires the beta 1-6-linked lactosamine antenna (beta 1-6 branch) for high affinity binding and was used in this study to quantitate these structures on glycoproteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Normal rodent tissues and cell lines were used to standardize the experimental conditions required to quantitate beta 1-6-branched oligosaccharide structures and the glycosyltransferase activity which initiates the synthesis of the antenna, beta 1-6 N-acetylglucosamine (GlcNAc)-transferase V (EC 2.4.1.155). Secondly, the levels of L-PHA-reactive oligosaccharide were compared in a series of benign and malignant human breast biopsies. Normal human breast tissue and benign lesions showed low expression but 50% of the primary malignancies examined showed significantly elevated L-PHA reactivity. GlcNAc transferase V activities in the human breast carcinomas and in normal murine tissues correlated with the levels of L-PHA reactive oligosaccharide in the tissues. GlcNAc transferase V showed similar ranges of activities, differing by approximately 5-fold between high and low expressing mouse tissues; fibroblasts with and without an activated H-ras oncogene; and low and high expressing human breast carcinomas. The results show that beta 1-6 branching in asparagine-linked oligosaccharides is dependent on tissue-specific regulation of GlcNAc transferase V activity. Secondly, a subset of human breast malignancies showed elevated levels of beta 1-6-branched oligosaccharides compared to benign samples, suggesting that further studies are warranted to determine whether the presence of these oligosaccharides is associated with metastatic disease and reduced patient survival time.
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PMID:Oncodevelopmental expression of--GlcNAc beta 1-6Man alpha 1-6Man beta 1--branched asparagine-linked oligosaccharides in murine tissues and human breast carcinomas. 252 56


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