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

In order to detect tumor-associated cellular proteins and to obtain information pertaining to the theory of an adenoma-carcinoma sequence, cellular proteins from mucosa, carcinoma, adenoma, carcinoma in adenoma, and polypoid carcinoma of the human colon were analyzed by two-dimensional (isoelectric focusing-SDS PAGE) electrophoresis. The results revealed the presence of about 300 spots with pIs from 5.5 to 8.5 and MWs from 20,000 to 200,000 in all of the five tissue types. The vast majority of them were common to these five tissue types. However, there were nine spots which differed between mucosa and carcinoma of the colon: Three spots (82/6.3, 65/8.2, 56/8.1, MW X 10(-3)/pI) were detected often in carcinoma but seldom in mucosa, and four spots (72/8.2, 72/8.5, 61/7.5, 38/6.5) were increased in amount in carcinoma. These seven spots could be the tumor-associated cellular proteins. The remaining two spots (31/7.2, 28/6.5), which were decreased in amount in carcinoma, were considered to be normal colon-associated cellular proteins. The three spots 82/6.3, 65/8.2 and 56/8.1 were also detected in adenoma, carcinoma in adenoma, and polypoid carcinoma. The four spots 72/8.2, 72/8.5, 61/7.5 and 38/6.5 were increased in amount in these three tissue types and spots 31/7.2 and 28/6.5 were decreased. The above results might provide evidence, though indirect, for the theory of an adenoma-carcinoma sequence.
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PMID:[A study of tumor-associated cellular proteins from carcinoma and adenoma of the human colon]. 360 May 90

The effect of the glycosylation inhibitor, tunicamycin, on synthesis and secretion of the membrane-associated glycoprotein carcinoembryonic antigen (CEA), was studied in the LS174T human colon cancer cell line. Tunicamycin treatment inhibited total cellular glycoprotein synthesis but did not affect CEA levels of cellular homogenate, membrane or cytosol fractions as determined by enzyme immunoassay. Control cells metabolically labelled with 3H-glucosamine, 3H-leucine or 35S-cysteine exhibited membranous and extracellular (i.e. secreted) CEA with an MW of 200 kDa as judged by SDS-gel electrophoresis following immunoprecipitation. However, in the tunicamycin-treated cells several forms of CEA with lower MWs and representing molecules with decreased glycosylation could be detected in addition to the original CEA molecule of 200 kDa present in control cells. The rates of synthesis, secretion and turnover of the lower-molecular-weight forms of poorly glycosylated CEA that appear after tunicamycin treatment are similar to those of CEA in control cells. These data suggest that the carbohydrate portion of the CEA molecule is not essential in synthesis, incorporation into the membrane, and secretion of CEA by colon cancer cells in vitro.
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PMID:Effect of tunicamycin on synthesis and secretion of carcinoembryonic antigen by human colonic adenocarcinoma cells. 373 60

The LAI reactivity of a colon organ specific neoantigen (OSN) was recovered from the urine of advanced colon cancer patients. In this study three physico-chemical steps were employed; precipitation by 80% ammonium sulfate, ion exchange, and molecular sieve chromatography. Each isolate was tested for activity and specificity by the direct tube leukocyte adherence inhibition (LAI) assay employing leukocytes from colon and breast cancer patients. The OSN enriched isolate was then used to generate monoclonal antibodies (Mab). Hybridomas were screened by ELISA. One hybridoma designated Bac 18.1 reacted preferentially with colon OSN and not with the urine from normals or patients with breast cancer. Affinity purification of colon OSN was achieved and it was shown to consist of a single band in SDS-PAGE with an apparent molecular weight of 30,000. The eluted polypeptide was specifically reactive in ELISA as well as in the LAI assay.
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PMID:The isolation of colon cancer organ specific neoantigen by the use of the leukocyte adherence inhibition assay and monoclonal antibodies. 375 60

Fucose-containing glycoproteins and glycolipids were compared in three human colon cancer cell lines and five human fetal intestinal epithelial cell lines. Cells were labeled by culturing cells in the presence of L-[3H]-fucose. Fucose was incorporated into both the membrane and cytoplasmic fractions of all three colon cancer cell lines to a much lesser extent than into fetal cells. When the relative fucose labeling of glycolipids and glycoproteins were examined, a much greater proportion of fucose labeling in the membrane was associated with lipid in colon cancer cells (11.6-16.7%) compared to fetal intestinal cells (1.3-2.5%). Fluorographic analysis of SDS-polyacrylamide gel electrophoresis of fucose-labeled glycoproteins revealed a rather uniform labeling pattern of fetal intestinal cells which was distinct from those of colon cancer cells. Thin-layer chromatographic analysis of fucose labeled glycolipids of all three colon cancer cell lines indicated the presence of fucose-containing glycolipids with carbohydrate chain lengths greater than five sugars. Glycolipids of the SKCO-1 cells in particular appear to consist predominantly of complex fucose-containing glycolipids. These results indicate that significant qualitative differences in the fucose-containing glycoproteins and glycolipids exist between the membranes of human colon cancer cells and fetal intestinal cells and that complex fuco-glycolipids with long carbohydrate side chains are present in the three human colon cancer cell lines.
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PMID:Membrane-associated, fucose-containing glycoproteins and glycolipids of cultured epithelial cells from human colonic adenocarcinoma and fetal intestine. 689 31

Organ-specific neoantigens (TA) shed from the tumours of patients with metastatic breast or colon cancer and which had filtered into the urine were partially purified by a combination of physicochemical methods and affinity chromatography. TA activity of the isolated materials was monitored by the blocking Tube LAI assay. Urinary protein was precipitated by 80% saturated ammonium sulphate. Albumin was removed by affinity chromatography with blue Sepharose CL-6B. Affinity columns of human IgG were prepared from sera of patients whose leucocytes were LAI+ to the breast- or colon-cancer extracts. The anti-breast-TA affinity column bound the TA in the urine of patients with metastatic breast cancer but not that of patients with metastatic colon cancer. The TA in urine of patients with metastatic colon cancer was bound by the anti-colon-TA affinity column. Analysis by SDS PAGE revealed that the isolates with and without TA activity were composed mostly of urinary protein which had bound nonspecifically to the human IgG affinity columns. With an affinity column of anti-NHS and Protein A, some of the contaminants were removed, to reveal SDD PAGE unique bands at about 38,000 and 12,000 mol. wt in the isolate with breast-TA activity. Rabbit antisera, raised to the material that had bound nonspecically to the anti-breast-TA affinity column, were used as an anti-nonspecific affinity column to remove the contaminants in the isolates from the affinity columns of anti-breast TA and anti-colon TA. After passage through the anti-nonspecific affinity column, the material that contained the putative breast or colon cancer TA revealed a unique band at about 38,000-40,000 mol. wt and residual fine bands at about 25,000-30,000 mol. wt. Both the control material and material with TA activity had similar bands at about 25,000 and 50,000 mol. wt. The specific activity of the putative colon or breast TAs, as measured by the blocking Tube LAI assay, was increased from about 30 to 5000-10,000 u/mg, a 125-400-fold enrichment.
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PMID:Partial purification of organ-specific neoantigens from human colon and breast cancer by affinity chromatography with human tumour-specific gamma-globulin. 736 81

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.
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PMID:Characterization of the major sialyl-Lex-positive mucins present in colon, colon carcinoma, and sera of patients with colorectal cancer. 785 Aug 10

We previously reported a new type of lectin, p33/41 (annexin IV), which was isolated from a bovine tissue extract [Kojima, K. et al. (1992) J. Biol. Chem. 267, 20536-20539]. When the expression of p33/41 (annexin IV) was surveyed in the lysates of 39 human tumor cell lines by SDS-PAGE, followed by Western blot analysis with polyclonal anti-bovine p33/41 and monoclonal anti-annexin IV (Z016, Zymed) antibodies, 21 cell lines were found to be reactive with the polyclonal antibody, whereas all 39 cell lines were stained with Z016. These results together with those obtained with standard proteins, annexins IV and V, suggested that the monoclonal antibody, Z016, recognizes annexin V, but not p33/41 (annexin IV). Therefore, we performed cDNA cloning of human p33/41 (annexin IV) to prepare a recombinant protein and raised monoclonal antibodies against the protein. Northern blot analysis with the cDNA as a probe showed that a human colon cancer cell line, HT29, contains p33/41 (annexin IV) mRNA of two sizes, 2.0 and 3.0 kb. The two monoclonal antibodies, AS11 and AS17, against the recombinant protein generated were useful for flow cytometric analysis, ELISA, Western blot analysis and immunoprecipitation. Flow cytometric analysis with AS17 showed that p33/41 (annexin IV) is located in the cytoplasm of HT29 cells, but not on the cell surface. However, one of the cell surface proteins first labeled with biotin and then solubilized with a detergent was immunoprecipitated with AS17. The results suggest the existence of a membrane spanning form of p33/41 (annexin IV).
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PMID:Expression of carbohydrate-binding protein p33/41 in human tumor cell lines. 888 29

Expression of the MUC2 mucin has been demonstrated in normal gastrointestinal and respiratory epithelium and in carcinomas of the gastrointestinal and respiratory tracts, breast, ovary, and bladder using RNA probes and (or) monoclonal antibodies reactive with peptide epitopes on the 23 amino acid tandem repeat. Mouse monoclonal antibodies 4F1 and 3A2 were previously obtained by immunization with mucin derived from the LS174T colon cancer cell line and a KLH conjugate of a synthetic MUC2 VNTR peptide. These antibodies react with distinct epitopes on synthetic VNTR peptides and with normal and malignant epithelial tissues. In the present study, we examined the biosynthesis of MUC2 in LS174T colon cancer cells, using these antibodies to immunoprecipitate labelled mucin. A very high molecular mass protein was immunoprecipitated following 1 min pulse labelling with [3H]threonine and [3H]proline. A slight increase in molecular mass was observed over the next 16 min; however, unlike the MUC1 mucin, there was no large difference in apparent molecular mass between the MUC2 protein precursor and fully processed mucin using separation by SDS-PAGE. O-Glycosylation began within 1 h of synthesis of the protein core. Mucin secretion into the culture medium was detected in the 2nd hour following synthesis and was largely completed within 4 h of synthesis. Secreted mucin was far less reactive with these monoclonal antibodies than the precursor protein.
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PMID:Early steps in the biosynthesis of MUC2 epithelial mucin in colon cancer cells. 903 93

High levels of bile acids in the colon may correlate with an increased risk of colon cancer, but the underlying mechanisms are not known. Proteoglycan structures have been shown to change when human colon cells differentiate in vitro. The expression of [(35)S]sulphated molecules was used as a phenotypic marker to study the effects of bile acids on the human-colon-carcinoma cell line CaCo-2. [(35)S]sulphated compounds were isolated from the medium of cell fractions of cells metabolically labelled with [(35)S]sulphate in the absence and presence of cholic acid, deoxycholic acid, chenodeoxycholic acid and lithocholic acid (LA). Labelled molecules were analysed by gel chromatography, HPLC and SDS/PAGE in combination with chemical and enzymic methods. The expression of (35)S-labelled proteoglycans was not affected by any of the bile acids tested. However, the level of sulphated metabolites increased 7-18-fold in different experiments during a 22 h labelling period in the presence of an LA concentration of 10 microg/ml (26.6 nmol/ml) compared with controls. Further analyses showed that this was due, at least in part, to the sulphation of LA itself. This sulphation of LA was a rapid process followed by secretion back to the medium. Brefeldin A did not reduce the sulphation of LA, indicating that this conversion takes place in the cytosol, rather than in the Golgi apparatus of the CaCo-2 cells. LA in colon may be sulphated efficiently by the colonocytes to reduce the toxic effects of this particular bile acid. Sulphation may possibly be an important protective mechanism in the colon.
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PMID:Sulphation of lithocholic acid in the colon-carcinoma cell line CaCo-2. 1052 30

Our previous studies have shown that the Galbeta1-3GalNAcalpha- (Thomsen-Friedenreich antigen)-binding lectin from the common edible mushroom Agaricus bisporus (ABL) reversibly inhibits cell proliferation, and this effect is a consequence of inhibition of nuclear localization sequence-dependent nuclear protein import after ABL internalization [Yu, L.G., Fernig, D.G., White, M.R.H., Spiller, D.G., Appleton, P., Evans, R.C., Grierson, I., Smith, J.A., Davies, H., Gerasimenko, O.V., Petersen, O.H., Milton, J.D. & Rhodes, J.M. (1999) J. Biol. Chem. 274, 4890-4899]. Here, we have investigated further the intracellular trafficking and fate of ABL after internalization in HT29 human colon cancer cells. Internalization of 125I-ABL occurred within 30 min of the lectin being bound to the cell surface. Subcellular fractionation after pulse labelling of the cells with 125I-ABL for 2 h at 4 degrees C followed by culture of the cells at 37 degrees C demonstrated a steady increase in radioactivity in a crude nuclear extract. The radioactivity in this extract reached a maximum after 10 h and declined after 20 h. Release of ABL from the cell, after pulse labelling, was assessed using both fluorescein isothiocyanate-labelled ABL and 125I-ABL and was slow, with a t1/2 of 48 h. Most of the 125I-ABL both inside cells and in the medium remained intact, as determined by trichloroacetic acid precipitation and SDS/PAGE, and after 48 h only 22 +/- 2% of ABL in the medium and 14 +/- 2% inside the cells was degraded. This study suggests that the reversibility of the antiproliferative effect of ABL is associated with its release from cells after internalization. The internalization and subsequent slow release, with little degradation of ABL, reflects the tendency of lectins to resist biodegradation and implies that other endogenous or exogenous lectins may be processed in this way by intestinal epithelial cells.
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PMID:Intracellular trafficking and release of intact edible mushroom lectin from HT29 human colon cancer cells. 1072 53


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