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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that peptides derived from the thrombospondin sequence, CSVTCG, promoted tumor cell adhesion. To further investigate this observation, the CSVTCG-tumor cell adhesion receptor from A549 human lung adenocarcinoma cells was isolated and characterized. A single protein peak was isolated by CSVTCG affinity chromatography which also analyzed as a single peak by anion exchange chromatography. The purified protein had a pI of 4.7 and analyzed on SDS-gels as a single band of M(r) = 50,000 under nonreducing conditions and as two protein bands of M(r) = 50,000, and 60,000 under reducing conditions. Purified CSVTCG binding protein (CBP) bound either CSVTCG- or TSP-Sepharose but showed little interaction with either VCTGSC- or BSA-Sepharose. CBP was cell surface exposed. CSVTCG derivatized with [125I] Bolton-Hunter reagent was taken up by cells in a dose-dependent manner and the cell association was inhibited with a monospecific polyclonal anti-CBP antibody. Examination of the cell proteins crosslinked to labeled CSVTCG by SDS-gel electrophoresis revealed one band that comigrated with purified CPB. Using an in vitro binding assay, purified CBP bound mannose, galactose, and glucosamine-specific lectins. CBP bound TSP saturably and reversibly. The binding was Ca+2/Mg+2 ion dependent and inhibited with fluid phase TSP and anti-CBP. Little or no binding was observed on BSA, fibronectin, GRGES, and GRGDS. Heparin, but not lactose, inhibited binding. Anti-CBP IgG and anti-CSVTCG peptide IgG inhibited A549 cell spreading and adhesion on TSP but not on fibronectin and laminin. These results indicate that CBP and the CSVTCG peptide domain of TSP can mediate TSP-promoted tumor cell adhesion.
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PMID:Identification and characterization of a tumor cell receptor for CSVTCG, a thrombospondin adhesive domain. 842 Oct 63

A galactoside-binding lectin (hL-31) containing a collagen-like sequence was identified in human tumor cells. It was found to be the homologue of the IgE-binding protein, the macrophage cell-surface Mac-2 antigen, and the murine CBP35, RL-29, and mL-34 lectins. Here we report on the expression in Escherichia coli and functional analysis of recombinant hL-31 (rhL-31). The rhL-31 was purified in one step through an asialofetuin affinity column. The rhL-31 was reactive to anti-lectin antibodies and retained its lactose-dependent hemagglutination of trypsin-treated glutaraldehyde-fixed rabbit erythrocytes. The rhL-31 elutes from an affinity column as a 31-kDa monomer and undergoes homodimerization at relatively high protein concentrations, comparable to those used to mediate hemagglutination. Electron microscopy showed that the rhL-31 appears as a Y-shaped structure. Lactoperoxidase-catalyzed iodination of murine tumor cell-surface proteins followed by collagenase treatment revealed that the lectin is probably a peripheral membrane protein whereby both the amino and the carboxy termini are exposed on the outer cell membrane. These results point to the membrane disposition and orientation of the lectin and suggest a mechanism for a structure-function relationship of lectin activity.
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PMID:Structure-function relationship of a recombinant human galactoside-binding protein. 847 70

The 67-kD laminin receptor (67LR) is a cell membrane-associated molecule exhibiting high affinity for the basement membrane glycoprotein, laminin. While export of the 67LR toward the extracellular matrix has been recently suggested by electron microscopy studies, there is to date no evidence of shedding of the 67LR from cells. Using two monoclonal antibodies directed against the 67LR, we developed a double-determinant radioimmunoassay that demonstrates that the 67LR is released from cancer cells into the culture medium. The shed molecule exhibited the same apparent molecular weight as that of the membrane-associated 67LR, suggesting that no proteolytic cleavage is involved in the process. Furthermore, we demonstrate that the 67LR is not anchored to the membrane through a glycolsyl-phosphatidylinositol bridge. However, the observation that lactose increased the release of 67LR suggests that a lectin-type interaction is involved in the cell membrane association of this laminin binding protein and the cell surface. Interestingly, the released 67LR recovered after HPLC gel filtration was found free as well as associated to high molecular weight complexes. The free 67LR retained its ability to bind to the cell surface. Our study is the first demonstration that the 67LR is effectively shed by cancer cells. The released free 67LR could play an important role in modulating interactions between cancer cells and laminin during tumor invasion and metastasis.
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PMID:Shedding of the 67-kD laminin receptor by human cancer cells. 865 33

Lectins from legumes constitute one of the most thoroughly studied families of proteins, yet the absence of a rigorous framework to explain their carbohydrate binding specificities appears to have prevented a rational approach to alter their ligand binding activity. Studies reported here deal with the redesign of the recognition propensity of peanut agglutinin (PNA), an important member of the family. PNA is extensively used as a tool for recognition of the tumor-associated Thomsen-Friedenrich antigen (T-antigen; Galbeta1-3GalNAc) on the surfaces of malignant cells and immature thymocytes. PNA also recognizes N-acetyllactosamine (LacNAc; Galbeta1-4GlcNAc), which is present at the termini of several cell-surface glycoproteins. The crystal structure of the PNA-lactose complex revealed, in addition to the expected interactions with the residues constituting the binding site, the presence of leucine 212 at a position close enough to be in steric contact with the acetamido group on LacNAc. We report here two leucine mutants, one to asparagine (L212N) and the other to alanine (L212A), that exhibit distinct preference for T-antigen and N-acetyllactosamine, respectively. Carbohydrate binding studies reveal that mutant L212N does not recognize LacNAc at high concentrations, thus making it an exquisitely specific cell-surface marker compared with its wild-type counterpart.
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PMID:Imparting exquisite specificity to peanut agglutinin for the tumor-associated Thomsen-Friedenreich antigen by redesign of its combining site. 870 92

We used several biotinylated neoglycoproteins as tumor markers to detect and localize endogenous carbohydrate-binding proteins in cultured hepatoblastoma, melanoma, and bladder carcinoma tumor cells. The neoglycoproteins used consisted of cellobiose, fucose, N-acetyl-galactosamine, N-acetyl-glucosamine, lactose, maltose, mannose, melibiose, and xylose. In addition, naturally occurring asialofetuin that was chemically disialylated was also used. Binding to the cultured tumor cells was made visible with the avidin-peroxidase technique. Depending on the type of neoglycoprotein used, markedly different expression of cytoplasmic and nuclear receptors for sugars (endogenous lectins) was obtained from rat hepatoblastoma, human melanoma, and bladder carcinoma tumor cells. The most pronounced staining differences were documented for asialofetuin and the neoglycoproteins containing fucose, N-acetyl-galactosamine, and lactose.
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PMID:Potential usefulness of biotinylated neoglycoproteins as tumor markers. 874 39

Galectin-3 is a beta-galactoside-specific lectin implicated in diverse processes involved in cellular interactions. Recently, the Mac-2-binding protein, a heavily N-glycosylated secreted protein with a subunit Mr of 97,000, was identified as its ligand. The present study characterizes the interaction between galectin-3 and Mac-2-binding protein in whole cells and measures their relative expression levels. Incubation of A375 cells with affinity-purified Mac-2-binding protein resulted in its binding to galectin-3 on the cell surface in a specific carbohydrate-dependent manner. Mac-2-binding protein also induced homotypic cell aggregation, which was inhibited by lactose or Fab' fragments of an anti-galectin-3 antibody. Northern blotting analysis revealed differences in the transcriptional regulation of galectin-3 and Mac-2-binding protein. These results provide the first direct evidence for a Mac-2-binding protein function and suggest that it may play a role in tumor cell embolization during metastasis through interaction with galectin-3.
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PMID:Interactions between galectin-3 and Mac-2-binding protein mediate cell-cell adhesion. 881 52

Comparative studies on the content of sialic acid and on the sialyltransferase activity in normal serum and in serum of rats with Zajdela ascitic hepatoma in different phases of tumor development have been conducted. Unlike the serum from animals with tumors, in which the sialic acid quantity increases in dependence of the stage of tumor development, the activity of serum sialyltransferase statistically augmented only in serum of rats at the final stage of tumor progression. The sialyltransferase activity towards asialofetuin as an acceptor in normal liver and in Zajdela hepatoma cells, was measured and a decrease in this activity in tumor cells as well as in host liver was found. When lactose was used as acceptor, again lower enzyme activity in the tumor cells in comparison with that in liver was established, but in liver and in hepatoma cells the predominant 14C-labelled product of the sialyltransferase assay was alpha (2-6) sialyllactose isomer. The results contribute to the biochemical characterization of rat Zajdela hepatoma.
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PMID:Activity and characterization of sialyltransferase from serum of normal rats, of rats bearing Zajdela ascitic hepatoma, in normal host liver and in Zajdela hepatoma cells. 884 9

Galectin-1, a member of a family of carbohydrate binding proteins, is synthesized by thymic epithelial cells in normal juvenile thymus, and mediates adhesion of immature T cells to thymic epithelium. Because cell adhesion molecules are proposed to play a role in the thymic hyperplasia and neoplasia seen in the autoimmune disease myasthenia gravis, we examined the expression of galectin-1 in myasthenic thymi. We detected abundant galectin-1 expression in thymic epithelial cells in 27 hyperplastic and neoplastic thymi from patients with myasthenia gravis. Primary cultures of neoplastic epithelial cells from a thymoma continued to express galectin-1, and bound immature T cells; T cell binding was inhibited by the addition of the beta-galactosides lactose and thiodigalactoside, suggesting that galectin-1 on the thymoma cells and a saccharide ligand on the T cells participated in cell-cell adhesion. Expression of galectin-1 by thymic epithelial cells may play a role in the thymic pathology seen in myasthenia gravis.
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PMID:Galectin-1 is expressed by thymic epithelial cells in myasthenia gravis. 887 16

Adhesion and spreading of tumor cells to the films of a galactose-, glucose-, or phosphatidylcholine-bearing lipid was studied. Human adenocarcinoma Hela cells, B16 mouse melanoma cells, and HuH-7 human hepatoma cells selectively adhered and spread on galactose-bearing lipid in serum-containing medium, but not in serum-free medium. The spreading of the tumor cells in serum-containing medium was inhibited in the presence of lactose, but not in the presence of maltose. Cell spreading also occured on the galactose-bearing glycolipid film pre-treated with serum. From quantitative analysis for the the adsorption of serum components by a quartz-crystal microbalance, the surfaces of the lipid films were found to be entirely covered with serum components. These results suggested that serum components pre-adsorbed on the galactose-bearing lipid influence the cell spreading.
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PMID:The influence of serum for spreading of tumor cells on synthetic glycolipid films. 892 25

Using autologous serum for the immunoscreening of a cDNA expression library derived from tissue involved by Hodgkin's disease, a new 36-kDa protein with the characteristics of galectins (S-type lectins) was detected. Sequence analysis of the cDNA clone HOM-HD-21 revealed two homologous motifs known as lectin domains with galactoside binding capacity. The two domains are linked by a stretch of about 30 amino acid residues and share a sequence homology of 39%. While the N-terminal lectin domain shows merely moderate homologies with known galectins, the C-terminal lectin domain is highly homologous to rat galectin-5 with an amino acid sequence identity of 70%. We ruled out mutations of the tumor-derived transcript by sequence comparison with the respective cDNA cloned from normal peripheral blood leukocytes. Recombinant protein expressed in Chinese hamster ovary cells was purified from lysates by lactose and galactose affinity chromatography, proving the galactoside binding capacity of this new galectin. Northern blot analysis revealed an expression spectrum restricted to peripheral blood leukocytes and lymphatic tissues. In accordance with the nomenclature of known galectins, we suggest to designate this novel galactoside binding protein galectin-9.
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PMID:Molecular definition of a novel human galectin which is immunogenic in patients with Hodgkin's disease. 904 65


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