Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adhesion of HT29 human colon adenocarcinoma cells to different extracellular matrix components was studied. While treatment of the cells with sialidase had no detectable effect on binding to laminin and fibronectin, attachment to collagen IV was decreased. However, additional removal of beta-(1-4)-bound galactose led to significantly reduced binding to all of the substrates, including fibronectin and laminin. Tunicamycin treatment, monitored by lectin-induced aggregation, drastically diminished cell adhesion to laminin and fibronectin, whereas cell binding to collagen IV was not affected. Arg-Gly-Asp (RGD)-related peptides were used to study the adhesion to collagen IV. The results show that a serine-containing RGD-related peptide GRGDSP has virtually no effect on colon carcinoma cell adhesion to type IV collagen. In contrast, when serine was substituted for threonine (GRGDTP) adhesion to collagen IV was strongly inhibited. After incubation of sialidase-treated cells with the threonine-containing peptide adhesion was almost totally blocked. These results demonstrate the existence of both RGD-dependent and carbohydrate-based mechanisms for metastatic human HT29 cell binding to collagen IV.
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PMID:Alterations in cell surface carbohydrate composition of a human colon carcinoma cell line affect adhesion to extracellular matrix components. 157 4

We collected a total of 78 tissue specimens, including primary colorectal carcinoma, normal colonic mucosa, and liver metastases of colon carcinoma, to examine whether the extracts of these tissues inhibited the binding of a monoclonal antibody FH6, specific for sialyl-dimeric LeX antigen. The results of inhibition assays demonstrated that: (a) contents of FH6-reactive molecules were greater in carcinoma tissues than in normal colonic mucosa; (b) metastatic foci in livers contained more FH6-reactive molecules than primary tumors; (c) primary tumors from Dukes' stage B1 patients contained less FH6-reactive molecules than primary tumors from Dukes' stage D patients. The inhibitory activity of these tumor tissue extracts against the binding of a monoclonal antibody FH6 to cultured colon carcinoma cells was eliminated by prior treatment of the extracts with sialidase, confirming that the FH6-reactive materials were sialyl-dimeric LeX antigen. Electrophoretic separation of tumor tissue extracts on 3% polyacrylamide gels followed by direct staining with monoclonal antibody FH6 revealed that very high molecular weight glycoproteins, presumably mucins, contained sialyl-dimeric LeX antigen.
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PMID:Increased expression of sialyl-dimeric LeX antigen in liver metastases of human colorectal carcinoma. 257 22

The colon carcinoma cell line COLO 205 has earlier been shown to express and secrete two mucin-type glycoproteins, the leukocyte-associated sialoglycoprotein CD43 or leukosialin (named L-CanAg) and the MUC1 mucin (named H-CanAg). Both glycoproteins carry sialyl-Lewis a epitopes and could bind transfected COS cells expressing E-selectin in a Ca(2+)- and E-selectin-dependent way. Using the monoclonal antibodies C50, C241 (both against sialyl-Lewis a), and CSLEX1 (against sialyl-Lewis x), the MUC1 mucin was shown to express both sialyl-Lewis a and sialyl-Lewis x epitopes, while the CD43 mucin expressed sialyl-Lewis a and almost no sialyl-Lewis x epitopes. These two secreted glycoproteins could inhibit human polymorphonuclear leukocyte or HL-60 cell adhesion to E-selectin-transfected COS cells or IL-1 beta-stimulated human endothelial cells in vitro. The inhibitory efficiency of the MUC1 mucin was 5-10 times larger than that of the CD43 mucin, when studied on endothelial cells and comparable amounts of sample were used. Removing the sialic acids from the MUC1 or CD43 mucins by sialidase treatment abolished the inhibitory effect. Monoclonal antibodies against sialyl-Lewis a greatly and equally inhibited the binding of the MUC1 or CD43 mucins, whereas an antibody against sialyl-Lewis x (CSLEX1) showed almost no inhibitory effect. The result proposes that the sialyl-Lewis a epitope on at least some mucin-type molecules bind E-selectin better than sialyl-Lewis x and that the potency of tumor-secreted mucins to interfere with leukocyte attachment to E-selectin could be dependent on the apoprotein size or its presentation of the carbohydrate epitopes.
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PMID:Comparison of sialyl-Lewis a-carrying CD43 and MUC1 mucins secreted from a colon carcinoma cell line for E-selectin binding and inhibition of leukocyte adhesion. 914 14

The cell surface glycosylation profiles of a liver metastatic colon carcinoma variant cell line, SL4 cells previously selected from colon 38 cells in vivo for liver colonization were investigated. Flowcytometric analysis was performed with 7 plant lectins and 10 carbohydrate specific monoclonal antibodies. The results showed that peanut agglutinin (PNA), Sambucus nigra agglutinin, Ulex europeus agglutinin-I, anti-LeX, anti-LeY, and anti-Le(b) antibodies bound to the parental colon 38 cells but not to SL4 cells. Another variant cell line was selected in vitro for the paucity of cell surface PNA-binding sites using a magnetic cell sorter and was designated as 38-N4 cells. The binding profiles of plant lectins and carbohydrate-specific antibodies to 38-N4 cells were very similar to those of SL4 cells. After intrasplenic injections, metastatic ability of 38-N4 cells was higher than that of colon 38 cells. PNA binding to SL4 cells and 38-N4 cells was detected after sialidase treatment of these cells, indicating increased sialylation of Thomsen-Friedenreich antigen in these cells. The mRNA levels of sialyltransferases, ST3Gal I, ST3Gal II, ST6GalNAc I, and ST6GalNAc II, were compared. The level of ST3Gal II mRNA was elevated in both SL4 cells and 38-N4 cells, whereas the level of ST6GalNAc II mRNA was elevated in 38-N4 cells compared with colon 38 cells. According to the expression array analysis, there are other glycosyltransferase genes differentially expressed between SL4 and colon 38 cells, yet their involvement in the altered glycosylation in these cells is unclear.
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PMID:Correlation between the sialylation of cell surface Thomsen-Friedenreich antigen and the metastatic potential of colon carcinoma cells in a mouse model. 1282 Jul 23

Selectin-mediated binding of tumor cells to platelets, leukocytes, and vascular endothelium may regulate their hematogenous spread in the microvasculature. We recently reported that CD44 variant isoforms (CD44v) on LS174T colon carcinoma cells possess selectin binding activity. Here we extended those findings by showing that T84 and Colo205 colon carcinoma cells bind selectins via sialidase-sensitive O-linked glycans presented on CD44v, independent of heparan and chondroitin sulfate. To assess the functional role of CD44v in selectin-mediated binding, we quantified the adhesion to selectins of T84 cell subpopulations sorted based on their CD44 expression levels and stable LS174T cell lines generated using CD44 short hairpin RNA. High versus low CD44-expressing T84 cells tethered more efficiently to P- and L-selectin, but not E-selectin, and rolled more slowly on P- and E-selectin. Knocking down CD44 expression on LS174T cells inhibited binding to P-selectin and increased rolling velocities over P- and L-selectin relative to control-transfected cells, without affecting tethering and rolling on E-selectin, however. Blot rolling analysis revealed the presence of alternative sialylated glycoproteins with molecular masses of approximately 170 and approximately 130 kDa, which can mediate selectin binding in CD44-knockdown cells. Heparin diminishes the avidity of colon carcinoma cells for P- and L-selectin, which may compromise integrin-mediated firm adhesion to host cells and mitigate metastasis. Our finding that CD44v is a functional P-selectin ligand on colon carcinoma provides a novel perspective on the enhanced metastatic potential associated with tumor CD44v overexpression and the role of selectins in metastasis.
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PMID:Selectin ligand expression regulates the initial vascular interactions of colon carcinoma cells: the roles of CD44v and alternative sialofucosylated selectin ligands. 1713 56