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)

Antibodies in ulcerative colitis (UC) serum promote antibody-dependent cellular cytotoxicity (ADCC) against colon cancer cells. The target molecules on the cells recognized by the antibody are unknown. This study examines the role of the M(r) 40K colon epithelial protein in this process. Serum from 29 UC patients, but not from 19 patients with Crohn's disease, significantly (p < 0.001) induced more cytotoxicity than did normal serum against DLD-1 colon cancer cells which are known to express the M(r) 40K protein. Peripheral blood lymphocytes but not polymorphonuclear leukocytes showed ADCC. Anti-M(r) 40K monoclonal antibodies significantly (p < 0.001) inhibited the UC-serum-induced ADCC, but not the spontaneous cytotoxicity. These results suggest the involvement of the M(r) 40K protein in ADCC induced by UC serum.
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PMID:Ulcerative colitis serum recognizes the M(r) 40K protein on colonic adenocarcinoma cells for antibody-dependent cellular cytotoxicity. 824 36

Human intestinal intraepithelial lymphocytes (IEL) demonstrate target cell-restricted spontaneous cytotoxic (SC) activity that is due to CD2+CD3+CD8+CD16-CD56- effector cells; they kill epithelial cell (EC) tumours (such as DLD-1 colon cancer cells), but not natural killer (NK)-sensitive K-562 cells. The present study shows that the measured levels of SC activities by IEL correlated with those of autologous lamina propria lymphocytes (LPL), but not with those of peripheral blood lymphocytes (PBL). Also, the susceptibilities of DLD-1 cell clones to lysis by IEL and PBL effector cells did not correlate, suggesting different mechanisms of lysis. Antibody blocking experiments showed that the main surface molecules involved in lysis depended on the effector cell type: alpha E beta 7 (HML-1) on IEL and CD16 on PBL. No antibody-dependent cell-mediated cytotoxicity (ADCC) was demonstrated by IEL, even after stimulation with interferon-gamma (IFN-gamma). Few IEL expressed Fc receptors for IgG. This study describes further differences between the SC activities of IEL and PBL.
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PMID:Spontaneous cytotoxicity of intestinal intraepithelial lymphocytes: clues to the mechanism. 750 97

Hepatocyte growth factor/scatter factor (HGF/SF) is a protein growth factor whose pleiotropic effects on epithelial cells include the stimulation of motility, mitosis and tubulogenesis. These responses are mediated by the cell surface tyrosine kinase receptor c-met. Because both the cytokine and receptor are found in the gastrointestinal tract, we have studied the effects of HGF/SF on transformed gut epithelial cells which express c-met. Here we describe the response of a new transformed human jejunal epithelioid cell line (HIE-7) to HGF/SF. Morphologically HIE-7 cells are immature. Their epithelial lineage was confirmed by reactivity with the epithelial specific antibodies AE1/AE3, Cam 5.2, Ber-EP4 and anti-EMA and is consistent with their expression of c-met mRNA and protein. In addition, electron microscopic analysis revealed the presence of primitive junctions and rudimentary microvilli, but features of polarization were absent. When grown on reconstituted basement membranes, HIE-7 cells formed closely associated multicellular cord-like structures adjacent to acellular spaces. However, the cells did not mature structurally, form lumen-like structures or express disaccharidase mRNA, even in the presence of recombinant HGF (rHGF). On the other hand, rHGF induced HIE-7 cells to scatter and stimulated their rapid migration in a modified wound assay. To determine whether the mitogenic effect caused by rHGF is associated with HIE-7 cell invasiveness across reconstituted basement membranes, a Boyden chamber chemoinvasion assay was performed. rHGF stimulated a 10-fold increase in the number of HIE-7 cells that crossed the basement membrane barrier, while only stimulating a small increase in chemotaxis across a collagen IV matrix, suggesting that the cytokine activates matrix penetration by these cells. rHGF also stimulated the invasion of basement membranes by an undifferentiated rat intestinal cell line (IEC-6) and by two human colon cancer cell lines which are poorly differentiated (DLD-1 and SW 948). In contrast, two moderately well differentiated colon cancer cell lines (Caco-2 and HT-29) did not manifest an invasive response when exposed to rHGF. These results suggest that HGF/SF may play a significant role in the invasive behavior of anaplastic and poorly differentiated gut epithelial tumors.
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PMID:Hepatocyte growth factor stimulates invasion across reconstituted basement membranes by a new human small intestinal cell line. 830 28

A culture system is presented in which a biologically more relevant substrate in the form of a collagen membrane and a biologically more relevant diffusion gradient system for nutrient delivery to the cells are provided. Five established human colon cancer cell lines (Caco-2, DLD-1, Widr, HCT 116 and HCT 8) were cultured in this system and three of them showed increased differentiation compared with the same cells cultured on the usual cell culture substrates of plastic and glass and with cells grown in an anchorage-independent manner. Caco-2 cells grow on plastic as a monolayer of large pleomorphic cells with scant mucin production. When cultured in a gradient diffusion system in a sandwich of type I/IV collagen the Caco-2 cells showed the highest degree of morphological and biochemical differentiation as evidenced by cellular alignment, glandular formation and mucin production. Similarly DLD-1 cells exhibited the greatest degree of morphological and biochemical differentiation in a gradient system in a type I/IV collagen sandwich. HCT 116 and HCT 8 cells, however, showed little change in differentiation phenotype under any of the 11 culture conditions tested. Widr cells grew in a type I/IV collagen sandwich in a gradient diffusion system as multilayered sheets of cells with intercellular spaces, suggestive of a moderate increase in differentiation phenotype. As judged by morphology and mucin production a range of differentiation capacities is exhibited by the five cell lines tested under the optimal differentiating culture conditions, with the order from most able to differentiate to least able to differentiate being Caco-2 > or = DLD-1 > or = Widr > HCT 116 > or = HCT 8.
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PMID:A defined collagen substrate and nutrient diffusion gradient culture system allows human colon cancer cells to assume a more differentiated phenotype. 835 94

Human intraepithelial lymphocytes (IEL), predominantly CD8+ T-lymphocytes located between intestinal epithelial cells (EC), may represent the first-line immune defense against colon cancer. The mechanism by which IEL bind to the colon cancer line, DLD-1, was evaluated. A larger fraction of IEL than peripheral blood mononuclear cells bound to DLD-1 monolayers (25 +/- 16 versus 8 +/- 4% binding, P < 0.05). Binding increased when DLD-1 monolayers were incubated with interferon-gamma but not with tumor necrosis factor-alpha. Similar numbers of IEL adhered to EC tumors, HT-29 and 5637, and the non-EC tumor, A375, but fewer bound to nonmalignant smooth muscle (HISM) and fibroblast (KD) lines (P < 0.01). Binding of IEL to DLD-1 was reduced by monoclonal antibodies to HML-1 and CD11a (47 +/- 9 and 26 +/- 13% inhibition, respectively) and was completely eliminated by both combined (93 +/- 4% inhibition). Anti-HML-1 also inhibited the binding of IEL to other EC tumors but did not affect binding to non-EC tumors or fibroblasts. To conclude, the binding of IEL to EC tumors is mediated by HML-1 and CD11a [A. I. Roberts, S. M. O'Connell, and E. C. Ebert. Binding of intraepithelial lymphocytes to colon cancer cells is mediated by HML-1 and LFA-1 (abstract). Gastroenterology, 102: A685, 1992].
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PMID:Intestinal intraepithelial lymphocytes bind to colon cancer cells by HML-1 and CD11a. 845 30

Genetic alterations of Ki-ras gene, p53 gene, and DCC gene were analyzed in human colon cancer cell lines (HCCLs). On the basis of these analyses, a HCCL (HCT116)-human chromosome 18 hybrids, and targeted cell lines that were disrupted at the activated Ki-ras gene in HCCLs (HCT116 and DLD-1), were established. Tumorigenicity and expression of c-myc gene were investigated in these cell lines, respectively. 1. Point mutations of Ki-ras gene, p53 gene, and insertion mutations of DCC gene were detected in 10 out of 18 HCCLs, 8 out of 15 HCCLs, and 3 out of 16 HCCLs, respectively. 2. HCT116-chromosome 18 hybrids were morphologically similar to the parental line, and were not suppressed for tumorigenicity in vitro, but they produced slowly growing tumors in nude mice compared with the growth of the parental line. 3. The targeted cell lines that were disrupted at the activated Ki-ras gene were morphologically altered and lost neoplastic phenotypes, including tumorigenicity in nude mice and anchorage-independent growth. Furthermore, expression of c-myc gene in these clones was much reduced compared with findings in the parental line, regardless of their growth rates.
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PMID:[Analysis of molecular mechanism in colorectal tumorigenesis]. 845 95

The elimination of tumor cells by cytotoxic T lymphocytes (CTLs) is, in part, executed by inducing apoptosis through the cell surface antigen Fas on the target cells. There are many cancer cells that resist Fas-mediated apoptosis. To elucidate the mechanism of this resistance is very important to understand the process of tumor development. We focused on FAP-1 (Fas-associated phos phatase-1), a negative regulator of Fas-mediated apoptosis. The expression of FAP-1 was detected in many colon cancer cell lines. On the other hand no FAP-1 expression was detected in the normal colon tissue. We have found that the tri-peptide of Fas C-terminus inhibited the binding of Fas and FAP-1 in vitro. Microinjection of the tri peptide (Ac SLV) could induce Fas-mediated apoptosis in the DLD 1 human colon cancer cell line that was resistant to anti-Fas-antibody. These findings suggest that the interaction of Fas and FAP-1 has a very important role in Fas-mediated apoptosis signal transduction. The inhibition of the Fas/ FAP-1 binding will provide a good target to develop anti-cancer drugs.
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PMID:[Development of anti cancer drugs targeted on Fas-mediated apoptosis signal]. 903 Feb 35

The tumor suppressor p53 protein induces apoptosis in response to various kinds of DNA damage in normal cells, but it is still unclear whether or not apoptosis induced by DNA damage correlates with the p53 status in tumor cells. We determined the status of p53 by functional analysis of separated alleles in yeast in five human colon cancer cell lines, SW-480, SW-620, DLD-1, COLO320 and LS174T and investigated whether p53 is necessary for apoptosis and cell cycle arrest after treatment of the cells with a DNA-damaging agent, etoposide (VP-16), or gamma-irradiation. Of these cell lines, only LS174T expresses a functional p53. Apoptosis was detected in SW-480 and COLO320 cell lines, but not in the other cell lines, including LS174T cell line with a normal p53 function. Furthermore, cell cycle analysis revealed accumulation in the G2M phase preceding induction of apoptosis in SW-480 and COLO320 cells, but not in the other cells. These results suggest that apoptotic induction by DNA damage is not necessarily related to p53 status and that induction of p53-independent apoptosis following DNA damage may correlate with G2M arrest in the cell cycle, at least in the colon cancer cell lines used in this study.
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PMID:Induction of p53-independent apoptosis associated with G2M arrest following DNA damage in human colon cancer cell lines. 904 94

Nonspecific cross-reacting antigen (NCA), a member of the carcinoembryonic antigen (CEA) family, shows increased expression levels in colorectal cancer tissues. To elucidate the mechanism, we observed the effect of interferon (IFN)-gamma on the expression level of NCA mRNA in colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction assay. IFN-gamma induced NCA mRNA in three of four cell lines tested. The effect of anti-fibronectin receptor (FnR) antibody on the expression of NCA mRNA was then examined in the same manner. Colo201 and DLD-1 cells showed an increased expression level of NCA mRNA after stimulation with the antibody. On flow cytometry, FnR was expressed in only two, Colo201 and DLD-1, of the five cell lines tested. These findings indicate that IFN-gamma and anti-FnR antibody induce NCA mRNA in cultured colon cancer cell lines, suggesting that inflammatory response and cell-to-extracellular matrix interaction may be related to the increased expression of NCA mRNA in colorectal cancers in vivo.
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PMID:Induction of nonspecific cross-reacting antigen mRNA by interferon-gamma and anti-fibronectin receptor antibody in colon cancer cells. 908 68

Ursodeoxycholate (UDCA) has anti-inflammatory and chemoprotective effects in animal models of inflammatory bowel disease and colon cancer. Because overproduction of nitric oxide (NO) by the inducible isoform of NO synthase (iNOS) is implicated in the pathogenesis of these conditions, we investigated the ability of UDCA to inhibit NO production in transformed human intestinal epithelial (DLD-1) cells. Nitrite/nitrate production was measured by the Griess reaction, enzymatic activity of iNOS was assessed by conversion of L-arginine to L-citrulline, and protein and mRNA were measured by Western and Northern blotting. Dose-dependent inhibition of interleukin-1 beta- and interferon-gamma-stimulated nitrite/nitrate production was observed when cells were preincubated for 6 h with UDCA (0-800 microM), and a substantial inhibition (81 +/- 3.2%) was seen at 500 microM. In cytokine-stimulated cells, UDCA reduced iNOS mRNA, protein, and enzyme activity without exerting cytotoxicity. UDCA had a minimal direct inhibitory effect on iNOS enzyme activity. UDCA pretreatment also reduced the expression of iNOS in the colonic epithelium of rats treated with bacterial lipopolysaccharide. Thus UDCA inhibits the induction of epithelial iNOS in vitro and in vivo, and this effect may contribute to the anti-inflammatory and chemoprotective actions of UDCA.
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PMID:Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo. 925 19


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