Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many cancer-associated antigens are present on mucin glycoproteins. These include peripheral antigens such as sialyl Lea and sialyl Lex and core region carbohydrate antigens such as T, Tn, and Sialyl Tn. We have recently described an inhibitor of mucin glycosylation, benzyl-alpha-GalNAc. The purpose of this study was to determine its effect on expression of mucin carbohydrate antigens. HM7 colon cancer cells were treated for 2 days in culture with 2 mM benzyl-alpha-GalNAc. This treatment did not affect viability or doubling time, but inhibited synthesis of [3H]glucosamine-labeled mucins. There was also secretion of benzyl-oligosaccharides and a decrease in the proportion of long oligosaccharides on 3H-labeled mucins. Mucins were purified from spent media by gel filtration and assayed for binding of monoclonal antibodies and lectins. Mucins from benzyl-alpha-GalNAc-treated cells had increased binding of peanut agglutinin (specific for T antigen, Gal beta 3GalNAc) and Vicia villosa agglutinin B4 (specific for Tn antigen, GalNAc alpha-Thr/Ser), but decreased binding of monoclonal antibodies 19-9, SNH3, and 91.9H (specific for sialyl Lea, sialyl Lex, and sulfomucin, respectively). Treatment of the cells with benzyl-alpha-GalNAc also decreased their binding to E-selectin (ELAM-1), which recognizes sialyl Lea and sialyl Lex. Thus, benzyl-alpha-GalNAc treatment, which decreases the level of peripheral carbohydrate carbohydrate antigens on mucins with accumulation of core region antigens, may be useful in modifying the immunological and biological properties of colon cancer cells.
 ...
PMID:Effect of benzyl-alpha-GalNAc, an inhibitor of mucin glycosylation, on cancer-associated antigens in human colon cancer cells. 128 81

Changes in the glycosylation of asparagine-linked oligosaccharides have been shown in various tumor cells, including human colon cancer. Attempts were made to elucidate the difference in Asn-linked oligo-saccharides attached to lysosomal membrane glycoproteins isolated from sublines of human colon carcinoma exhibiting high and low metastatic potentials in nude mice. Lysosomal membrane glycoproteins (lamp) 1 and 2 were immunoprecipitated from the cells after labeling with radioactive sugars, and the glycopeptides prepared were fractionated by serial lectin affinity chromatography employing immobilized concanavalin A, Datura stramonium agglutinin, and tomato lectin. Comparison of Asn-linked oligosaccharides from the different colonic carcinoma cells revealed the following features. First, the highly metastatic carcinoma cells express more poly-N-acetyllactosaminyl side chains with branched galactose residues than cells with low metastatic potential. Second, sialylation is more significant in the highly metastatic carcinoma cells than in the poorly metastatic ones. Conversely, N-acetyllactosamine units are less fucosylated in the highly metastatic cells than in poorly metastatic cells. These structural changes were apparently caused by the increase in sialyltransferase and the decrease in alpha 1----3 fucosyltransferase in the highly metastatic cells. The results also suggest that highly metastatic carcinoma cells express more sialyl Lex structures at the termini of poly-N-acetyllactosaminyl side chains than poorly metastatic carcinoma cells. Further, highly metastatic cells were found to express more lamp-1 and lamp-2 on the cell surface. These results were found to be correlated to the increased expression of sialyl Lex structures with high affinity binding of anti-sialyl Lex antibody on highly metastatic cells. Increased expression of sialyl Lex in the poly-N-acetyllactosamines of the cell surface may contribute to the metastatic behavior of the cells, assuming that this structure can serve as a better ligand for selectins present on endothelial cells and platelets.
 ...
PMID:Differential glycosylation and cell surface expression of lysosomal membrane glycoproteins in sublines of a human colon cancer exhibiting distinct metastatic potentials. 154 42

Oligosaccharides with Lex determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc) are accumulated in large quantities in various adenocarcinomas. Monoclonal antibodies recognizing mono-, di-, or trimeric Lex showed a preferential staining of specific stages of human fetal tissues and various human adenocarcinomas. Thus, these carbohydrate epitopes are typical of oncodevelopmental antigens. The present study investigated the presence of Lex epitope in sera of normal individuals and cancer patients, utilizing two high-affinity monoclonal antibodies, SH1 and SH2, directed to mono- and dimeric Lex structures, respectively. The Lex antigen in serum was eluted in the void volume fraction of a gel filtration column, determined by using monoclonal antibody SH1, and found to be carried on a glycoprotein with a molecular weight of approximately 200,000. The Lex antigen was present in the void volume fraction of the majority (85%) of sera from adenocarcinoma patients. Although the Lex epitope was also detected in a smaller proportion (33%) of normal sera, its levels were significantly lower than in cancer sera. Lex antigen was also detected in serum glycolipid fraction; however, no significant differences were observed in normal and cancer sera. A double determinant solid phase immunoassay utilizing SH2 as the capture antibody and SH1 as the detecting antibody allowed direct determination of Lex levels in sera. By the use of this direct assay, the levels of serum Lex were found to increase in association with the progression of colorectal cancer (Dukes A to D). The percentage of detectability in sera from colon cancer patients was as follows: Dukes A, 20%; Dukes B, 45%; Dukes C, 67%; and Dukes D, 74%. The levels of serum Lex were also of prognostic value in Dukes C cancer patients after surgery and during postoperative follow-up.
 ...
PMID:Profiles of Lewisx-containing glycoproteins and glycolipids in sera of patients with adenocarcinoma. 230 2

The monoclonal antibody NCC-CO-450 (IgM kappa) was selected by screening of reactivity with high-molecular-weight antigens (Mr greater than 10(6] isolated from ascitic fluid of a colon cancer patient. This antibody detected heterogeneous but predominantly high-molecular-weight antigens in 4 of 6 ascitic fluid samples from gastrointestinal cancer patients by immunoblotting analysis. A sandwich radioimmunoassay was developed in order to examine the serum level of this antigen, and the cutoff value was defined as the mean plus 2 SD of values obtained with sera from normal donors. While 97% (93 of 96) of sera had a negative antigen value in normal donors, 56% (14 of 25) of patients with colorectal carcinoma and 40% (8 of 20) of patients with gastric carcinoma showed a positive antigen value. The distribution of the antigen in sera of patients with various cancers did not show any correlation with the distribution of carcinoembryonic antigen or CA 19-9. From immunohistochemical and biochemical analyses, NCC-CO-450 antigen was characterized as a mucin-like glycoprotein abundant in normal colonic epithelium as well as in carcinomas of the colon, stomach, and pancreas. The immunohistochemical reactivity of NCC-CO-450 was distinct from that of other monoclonal antibodies reported to be useful for serological diagnosis. The epitope recognized by NCC-CO-450 is considered to be an O-linked carbohydrate chain without terminal sialic acid but is different from the known carbohydrate chains, i.e., Lea, Lex, LeY, Tn, sialyl-Lea, and sialyl sugar chain defined by NCC-ST-439 in a competitive binding inhibition assay of monoclonal antibodies. This newly defined antigen is a good example of a normal antigen shed from cancer cells that can be used successfully as a serum tumor marker.
 ...
PMID:Selection of a monoclonal antibody reactive with a high-molecular-weight glycoprotein circulating in the body fluid of gastrointestinal cancer patients. 245 34

Two mouse monoclonal antibodies (MoAbs), KM-93 raised against human lung adenocarcinoma and KM-231 raised against human gastric cancer, were useful in serum diagnosis of several human cancer. KM-93 and KM-231 recognize sialyl Lex epitope and sialyl Lea epitope, respectively, expressed on glycoprotein and glycolipid. We established a new "cocktail" sandwich enzyme-linked immunosorbent assay system using the two MoAbs and the advantage of this assay system, which can simultaneously detect sialyl Lex and sialyl Lea antigens, is assessed in the present study. The new assay system is composed of a mixture of KM-93 and KM-231 as 1st antibodies and a mixture of biotinylated two MoAbs as 2nd antibodies. We evaluated the concentration of MoAbs and optimized it to gain high cancer-positivity. This assay system covered sialyl Lex positive and/or sialyl Lea-positive sera and gave a high rate of positive results in lung adenocarcinoma (62.3%), gastric cancer (32.5%), colon cancer (37.5%), pancreatic cancer (83.3%), bile duct and gall bladder cancer (66.7%) and hepatoma (76.9%), whereas positive results in healthy adults remained low. Positive results in benign diseases of lung (12.5%), pancreas (10.8%), gall bladder and bile duct (9.1%) were very low, but were higher in liver cirrhosis (33.3%), hepatitis and liver injury (34.8%). Simultaneous detection of two carbohydrate antigens, sialyl Lex and sialyl Lea was clearly superior to single detection.
 ...
PMID:Advantage of cocktail-use of two anti-tumor monoclonal antibodies, KM-93 and KM-231, in serum diagnosis of cancer. 247 31

Recently E-selectin (ELAM-1, endothelial leukocyte adhesion molecule-1) was shown to recognize not only sialyl Lewis X but also sialyl Lewis A, and these carbohydrate antigens may be involved in the process of the adhesion between cancer cells and endothelial cells in cancer metastasis. To investigate the contribution of sialylated carbohydrate antigen, SPan-1, and sialic acid to the adhesion of human colon cancer cells to endothelial cells, adhesion assay using HUVECs (human umbilical vein endothelial cells) was performed. The adhesion was significantly inhibited by pretreatment with anti-E-selectin antibody, indicating that this adhesion was thought to be mediated by E-selectin. When these cancer cells were pretreated with SPan-1 antibody, the adhesion was significantly inhibited in a concentration-dependent manner. The adhesion was also inhibited by pretreatment with neuraminidase. These findings suggest that the SPan-1 antigen plays a significant role in the adhesion of human colon cancer cells to endothelial cells, and sialylation of the terminal structure of carbohydrate antigens is important in this adhesion.
 ...
PMID:Role of SPan-1 antigen in adhesion of human colon cancer cells to vascular endothelium. 753 92

Previous studies from our laboratory have shown that benzyl-alpha-GalNAc inhibits the glycosylation of mucin in colon cancer cells. In this study, we determined whether benzyl-alpha-GalNAc inhibits mucin glycosylation in KATO III gastric cancer cells. We also examined its effects on expression of mucin antigens, and compared the mucins made by KATO III with those of a colonic cancer cell line, Caco-2. Results of these experiments suggest that benzyl-alpha-GalNAc (2 mM) inhibited [3H]glucosamine labelling of mucins by 82% in KATO III and by 70% in Caco-2. For both cell lines, the mucin secreted in the presence of benzyl-alpha-GalNAc was less acidic. Both cell lines secreted benzyl-oligosaccharides, but those from KATO III (8-9 sugars) were larger than those from Caco-2 (6-7 sugars). In mucins purified from the medium of treated cells, peripheral carbohydrate antigens (sialyl Lex in KATO III and terminal fucose in Caco-2) were decreased (compared with control), while core carbohydrate antigens (T antigen in both cell lines and sialyl Tn in Caco-2) were increased. Western blots of cell homogenates showed differences between KATO III and Caco-2 in MUC 1 apomucin protein antigens, in sialyl Lex and in sialyl Tn antigens. We conclude that benzyl-alpha-GalNAc does inhibit the glycosylation of mucin in KATO III gastric cancer cells as in human colon cancer cells, but that alterations in mucin antigens occur in a cell line-specific manner.
 ...
PMID:Inhibition of mucin synthesis by benzyl-alpha-GalNAc in KATO III gastric cancer and Caco-2 colon cancer cells. 757 79

Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (O-glycans). To elucidate the control of the biosynthesis of these O-glycans is colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated O-glycan structures. We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of O-glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-Tn, T and Lex antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R beta 3-N-acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAc beta 1-3GalNAc-, CMP-sialic acid: GalNAc-peptide alpha 6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Gal beta 1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Gal beta 1-3GalNAc beta 6-N-acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAc beta 1-6(GlcNAc beta 1-3) GalNAc-, CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase and GDP-fucose: Gal beta-R alpha 2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue. The data suggest that the biosynthesis of antigens and mucin-bound O-glycan structures in colon cancer is subject to complex control mechanisms.
 ...
PMID:Alterations of O-glycan biosynthesis in human colon cancer tissues. 773 50

The expression of the mucin-bound sialyl-Lewisx epitope is increased in the tissue of most colorectal carcinomas and in the sera of about 30% of tumor patients. In colon cancer, a portion of the sialyl-Lex groups detectable with the monoclonal antibody AM-3 is located on MUC1 (C. Hanski et al., Cancer Res., 53: 4082-4088, 1993). In order to characterize the major colon carcinoma-associated sialyl-Lex-positive glycoprotein components, the tissue- and serum-derived antigens were investigated. The buoyant densities of the sialyl-Lewisx-positive antigens from tumor and normal colonic tissues and from sera of patients with colon carcinoma and healthy donors correspond to that of mucins (1.40 g/ml). The sialyl-Lex-positive mucins purified from both tissues elute under nonreducing conditions in the void volume of a Sepharose CL-2B column, indicating a molecular mass more than 2 x 10(7) daltons. They yield in immunoblot after SDS gel electrophoresis under reducing conditions a main band at an apparent M(r) 880,000. Radioactive labeling revealed that the band at M(r) 880,000 is the major protein component in sialyl-Lewisx-positive mucins both from tumor and normal colonic tissue. In sera of colon carcinoma patients, the sialyl-Lex moiety is also detectable mainly on a M(r) 880,000 glycoprotein band and, additionally, on a M(r) 140,000 molecule as well as on alpha 1-acid glycoprotein. Sera from healthy donors exhibited only a sialyl-Lex-positive glycoprotein with the apparent M(r) 140,000. Sandwich ELISA as well as immunoblots of mucins purified from the colon carcinoma cell line LS174T indicated that the sialyl-Lex moiety migrating in the M(r) 880,000 band is located on MUC2 protein core. Together, these data suggest that sialyl-Lex antigen in colon, colon carcinoma, and the sera of patients with this tumor is located on the MUC2 molecule, consisting of several subunits with an apparent M(r) 880,000, linked via disulfide bridges. The increase of sialyl-Lex expression in colon carcinomas appears to be mainly due to a more frequent transfer of sialyl-Lex moieties onto the mucin core in tumor tissue.
 ...
PMID:Characterization of the major sialyl-Lex-positive mucins present in colon, colon carcinoma, and sera of patients with colorectal cancer. 785 Aug 10

A comparative immunohistochemical study was performed to analyse the expression of cancer-associated carbohydrate antigens by primary and metastatic lesions of colon cancer. We used monoclonal antibodies which reacted with Lea, Lex and Tn as well as their sialylated derivatives. Twenty-one primary lesions in patients without metastasis and 26 primary and metastatic lesions in patients with liver metastasis were studied. Sialyl Lea was expressed by 57% of the primary lesions of patients without metastasis, 65% of the primary lesions of patients with metastasis and 73% of their liver metastases. Sialyl Lex was expressed by 60% of the primary lesions of patients with and without metastasis as well as by approximately 80% of the liver metastases. Sialyl Lea and sialyl Lex showed strong expressions in the liver metastases, significantly greater than in the primary lesions. The findings indicate the increased expressions of sialyl Lea and sialyl Lex to be correlated with liver metastasis of colorectal cancer.
 ...
PMID:Carbohydrate antigens and liver metastasis in colorectal cancer. 790 24


1 2 3 Next >>