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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two types of human fibroblasts have been isolated from a patient with a colon cancer with metastasis, one type was derived from a healthy part of the colon, and the other one isolated from a metastasized lymph node close to the intestine. These fibroblasts have been characterized for their expression of collagens type I, III and IV, vimentin, fibronectin, alpha-smooth muscle actin, laminin and desmin. The effects of conditioned media of human colon cancer cell lines, HT29, SW1116, LS180 and HCT8R, on the metabolism of these fibroblasts were tested. All the conditioned media stimulate both types of fibroblasts, as reflected by their incorporation of radiolabelled methionine and proline. Normal fibroblasts were highly sensitive to the conditioned media as compared to the activated fibroblasts. Additionally, the production of TGF beta 1 by the four colorectal cancer cell lines has been quantified, and significant qualitative (production of latent and/or active form) and quantitative differences were observed. The effects of the conditioned media of the four tumoral cell lines and exogenous TGF beta 1 on the proliferation of the two types of fibroblasts were compared. Our data indicated that the two types of fibroblasts respond differently to TGF beta 1 whereas they are both growth stimulated by the conditioned media, apart from the LS180 conditioned medium. We conclude that if TGF beta 1 acts in the fibroblastic reaction, additional factors are required.
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PMID:[Role of TGF beta 1 in the stromal reaction to human colonic tumors]. 817 75

Hepatocyte growth factor (HGF), also known as scatter factor, regulates both cell motility and the growth of some cell types. We have determined the effects of HGF on the motility and growth of human colon cancer cell lines (HT115, HT29, HRT18 and HT55). Cell motility, as measured by dissociation from carrier beads or by scattering of cell colonies, was greatly increased in all cell lines. The effects were completely blocked by anti-HGF antibody. In contrast, cell growth of HT115, HT29 and HRT18 cells was inhibited by a wide range of concentrations of HGF. HT55 cell growth was also inhibited but needed a prolonged culture period (> 5 days). The HGF receptor/Met protein is highly expressed in the membrane fraction of these cells as determined by Western blotting. It is concluded that HGF has an effect on both colon cancer cell motility and growth, which may be important in the control of the spread of colon cancer.
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PMID:Regulation of spreading and growth of colon cancer cells by hepatocyte growth factor. 838 69

The effects of fluorouracil (5-FU) and interferon-gamma (IFN-gamma) on the regulation of thymidylate synthase (TS) gene expression were investigated in the human colon cancer H630 cell line. By Western immunoblot analysis, TS protein levels in H630 cells were increased 3-, 5.5-, 5-, and 2.5-fold after 8-, 16-, 24-, and 36-hr exposure to 1 microM 5-FU, respectively. When H630 cells were exposed to varying concentrations of 5-FU (0.3-10 microM) for 24 hr, increases in TS protein up to 5.5-fold were observed. A 24-hr exposure to 1 microM 5-FU resulted in a 4.5-fold increase in the level of TS protein, whereas in 5-FU/IFN-gamma-treated cells TS protein was increased by only 1.8-fold, compared with control cells. IFN-gamma treatment alone did not affect TS protein levels, relative to control. Northern blot analysis revealed no changes in TS mRNA levels when H630 cells were exposed either to 1 microM 5-FU for 8-36 hr, to varying concentrations of 5-FU (0.3-10 microM) for 24 hr, or to the combination of 5-FU and IFN-gamma. Pulse-labeling studies with [35S]methionine demonstrated a 3.5-fold increase in net synthesis of TS in cells treated with 1 microM 5-FU, whereas the level of newly synthesized TS increased only 1.5-fold in cells treated with 5-FU/IFN-gamma, compared with control cells. Pulse-chase studies revealed that the half-lives of TS protein in control and 5-FU-treated cells were equivalent. These findings demonstrate that the increase in TS protein after 5-FU exposure and the subsequent inhibitory effect of IFN-gamma on TS protein expression are both regulated at the post-transcriptional level.
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PMID:Regulation of thymidylate synthase in human colon cancer cells treated with 5-fluorouracil and interferon-gamma. 847 31

A plasma membrane preparation from human amnion (WISH) cells contained uridine diphosphate sugars and methyl-uridine diphosphate (mUDP) sugars. The synthesis of mUDP-glucose, mUDP-mannose, and mUDP-fucose by the membrane preparation occurred when supplemented with uridine-5'-diphosphate-glucose and S-adenosyl-L-methionine. It is suggested that this newly recognized route for fucose biosynthesis might be employed by certain transformed cells, and may partly account for the methionine dependence of certain human tumors. Additionally, it is suggested that, in colon cancer, a deficiency of folic acid and methionine might affect mUDP-sugar biosynthesis rather than the methylation of DNA.
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PMID:Involvement of methionine in the synthesis of certain membrane-associated nucleotide sugars by human amnion (WISH) cells. 862 Apr 51

Evidence is accumulating that folate, a B vitamin found in green leafy vegetables, may affect the development of neoplasia. We examined the relationship between folate status and colorectal cancer in a case-control study nested within the Alpha-Tocopherol Beta-Carotene Study cohort of male smokers 50-69 years old. Serum folate was measured in 144 incident cases (91 colon, 53 rectum) and 276 controls matched to cases on baseline age, clinic, and time of blood collection. Baseline dietary folate was available from a food-use questionnaire for 386 of these men (92%). Conditional logistic regression modeling was used. No statistically significant association was observed between serum folate and colon or rectal cancer. Although a 2-fold increase in rectal cancer risk was suggested for men with serum folate > 2.9 ng/ml and those in the highest quartile of energy-adjusted folate intake, there was no evidence of a monotonic dose-response, and all confidence intervals included unity. For dietary folate and colon cancer, odds ratios of 0.40 [95% confidence interval (CI), 0.16-0.96], 0.34 (95% CI, 0.13-0.88), and 0.51 (95% CI, 0.20-1.31) were obtained for the second through fourth quartiles of energy-adjusted folate intake, respectively, compared to the first (P for trend = 0.15). Furthermore, men with a high-alcohol, low-folate, low-protein diet were at higher risk for colon cancer than men who consumed a low-alcohol, high-folate, high-protein diet (OR, 4.79; 95% CI, 1.36-16.93). This study suggests a possible association between low folate intake and increased risk of colon cancer (but not rectal cancer) and highlights the need for further studies that measure dietary folate and methionine, along with biochemical measures of folate (i.e., erythrocyte and serum), homocysteine, and vitamin B12.
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PMID:Colorectal cancer and folate status: a nested case-control study among male smokers. 882 51

Little is known about the the signalling pathways driving the adenoma-to-carcinoma sequence in human colonic epithelial cells. Accumulation and activation of the src tyrosine kinase in colon cancer suggest a potential role of this oncogene in this early progression. Therefore, we introduced either activated src (m-src), polyoma-MT alone or combined with normal c-src in the adenoma PC/AA/C1 cell line (PC) to define the function and phenotypic transformations induced by these oncogenes in familial adenomatous polyposis (FAP) colonic epithelial cells. Functional expression of these oncoproteins induced the adenoma-to-carcinoma conversion, overexpression of the hepatocyte growth factor (HGF) receptor Met, but failed to confer invasiveness in vivo and in vitro, or to produce alterations in cell proliferation and differentiation. In contrast, PC-msrc cells became susceptible to the HGF-induced invasion of collagen gels and exhibited sustained activation of the pp60src tyrosine kinase and Tyr phosphorylation of the 120-kDa E-cadherin, which was further increased by HGF Transcripts of HGF were clearly identified by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot in the parental and transformed PC cells, suggesting an autocrine mechanism. Taken together, the data indicate that: (1) experimental activation of src and PyMT pathways directly induces tumorigenicity and Met upregulation in a colon adenoma cell line; (2) HGF-activated Met and src cooperate in inducing invasion; (3) in view of the molecular associations between catenins and cadherin or the tumour-suppressor gene product APC, the cell adhesion molecule E-cadherin may constitute a downstream effector of src and Met.
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PMID:Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion. 901 33

Folate derivatives are important in experimental colorectal carcinogenesis; low folate intake, particularly with substantial alcohol intake, is associated with increased risk. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate, required for purine and thymidine syntheses, to 5-methyltetrahydrofolate, the primary circulatory form of folate necessary for methionine synthesis. A common mutation (677C-->T) in MTHFR reduces enzyme activity, leading to lower levels of 5-methyltetrahydrofolate. To evaluate the role of folate metabolism in human carcinogenesis, we examined the associations of MTHFR mutation, plasma folate levels, and their interaction with risk of colon cancer. We also examined the interaction between genotype and alcohol intake. We used a nested case-control design within the Physicians' Health Study. Participants were ages 40-84 at baseline when alcohol intake was ascertained and blood samples were drawn. During 12 years of follow-up, we identified 202 colorectal cancer cases and matched them to 326 cancer-free controls by age and smoking status. We genotyped for the MTHFR polymorphism and measured plasma folate levels. Men with the homozygous mutation (15% in controls) had half the risk of colorectal cancer [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27-0.87] compared with the homozygous normal or heterozygous genotypes. Overall, we observed a marginal significant increased risk of colorectal cancer (OR, 1.78; 95% CI, 0.93-3.42) among those whose plasma folate levels indicated deficiency (<3 ng/ml) compared with men with adequate folate levels. Among men with adequate folate levels, we observed a 3-fold decrease in risk (OR, 0.32; 95% CI, 0.15-0.68) among men with the homozygous mutation compared with those with the homozygous normal or heterozygous genotypes. However, the protection due to the mutation was absent in men with folate deficiency. In men with the homozygous normal genotype who drank little or no alcohol as reference, those with the homozygous mutation who drank little or no alcohol had an 8-fold decrease in risk (OR, 0.12; 95% CI, 0.03-0.57), and for moderate drinkers, a 2-fold decrease in risk (OR, 0.42; 95% CI, 0.15-1.20); no decrease in risk was seen in those drinking 1 or more drinks/day. Our findings provide support for an important role of folate metabolism in colon carcinogenesis. In particular, these results suggest that the 677C-->IT mutation in MTHFR reduces colon cancer risk, perhaps by increasing 5,10-methylenetetrahydrofolate levels for DNA synthesis, but that low folate intake or high alcohol consumption may negate some of the protective effect.
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PMID:Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. 906 78

Disturbances in DNA methylation have been hypothesized as being involved in carcinogenesis. It has been proposed that dietary factors such as folate, alcohol, and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large retrospective population-based case-control study of incident colon cancer were used to evaluate whether intake of alcohol and other dietary factors involved in DNA methylation are associated with colon cancer. Dietary data were obtained using a detailed diet history questionnaire. We did not observe strong independent associations between folate, vitamin B6, vitamin B12, methionine, or alcohol and risk of colon cancer after adjusting for body size, physical activity, cigarette smoking patterns, energy intake, and dietary intake of fiber and calcium. However, when assessing the associations between colon cancer and a composite dietary profile based on alcohol intake, methionine, folate, vitamin B12, and vitamin B6, we observed a trend of increasing risk as one moved from a low- to a high-risk group. This trend was modest and most marked in those diagnosed at a younger age [odds ratio (OR) for men = 1.3, 95% confidence interval (CI) = 0.9-1.9; OR for women = 1.6, 95% CI = 1.0-2.6]. We observed that associations with this high-risk dietary profile were greater among those who took aspirin or nonsteroidal anti-inflammatory drugs on a regular basis and were younger at the time of diagnosis (men OR = 1.7, 95% CI = 1.0-3.2; women OR = 2.2, 95% CI = 1.0-4.8) and for distal tumors (men OR = 1.4, 95% CI = 0.9-2.3; women OR = 2.0, 95% CI = 1.0-3.8). Findings from this study provide only limited support for previously reported associations between dietary factors involved in DNA methylation and risk of colon cancer.
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PMID:Are dietary factors involved in DNA methylation associated with colon cancer? 920 Jan 51

We have compared the expression of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in ten paired samples of normal and tumour colonic tissue with regard to both mRNA and protein. We have compared sensitivity of these tissues to IGF-I using primary cultures of epithelial cells of colonic mucosa, and we have examined the production of IGFs and IGFBPs by these cells. In the tissues, IGFBP-2 mRNA was expressed in all normal and cancer samples but other IGFBPs showed variable expression. mRNAs for IGF-I were expressed in all normal and cancer tissues but IGF-II mRNA was only detected in cancer tissue (3 out of 10). Immunostaining of sections of normal and cancer tissue was negative for IGF-I and IGF-II; IGFBP-2 was positive in 2 out of 10 cancer tissues and 7 out of 10 normal tissues; IGFBP-3 was positive in 7 out of 10 cancer tissues and 7 out of 10 normal tissues; and IGFBP-4 was positive in 5 out of 10 cancer tissues and 6 out of 10 normal tissues. In the cells in culture, cancer cells showed increased incorporation of [35S]methionine into protein and [3H]thymidine into DNA (P < 0.02) when treated with IGF-I. Western blotting of serum-free conditioned media from cells in culture showed that 8 out of 10 normal and 3 out of 10 cancer cultures produced a 32-kDa immunoreactive IGFBP-2. No IGFBP-3 was secreted by any culture but 24-kDa IGFBP-4 was found in 3 out of 10 normal and 5 out of 10 cancer tissues. Because of the discrepancy between mRNA and protein expression for IGFBP-2, degradation of native IGFBPs was assessed using tissue extracts. Colon cancer extracts were able to degrade exogenous IGFBP-2, IGFBP-3 and IGFBP-4, whereas normal tissue extracts were without effect on IGFBP-2. We conclude that IGFBPs are synthesized and secreted by cells of the colonic mucosa but that proteolysis of secreted IGFBP-2 occurs in colon cancer tissue. This selective degradation may confer a growth advantage.
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PMID:Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers. 921 34

Colon carcinoma cells provide a useful model to study the biochemical processes associated with cell differentiation. Undifferentiated HT29, differentiated HT29MTX(-3) and HT29MTX(-6), and Caco2 human colon carcinoma cells have been used to study the production of proteoglycans and to characterize the glycosaminoglycan structure of the heparan sulphate chains. All the cell lines produce mainly a heparan sulphate proteoglycan that is found partly in the extracellular medium and associated to the cell membrane. The heparan sulphate proteoglycans from the media were purified by ion-exchange chromatography and subjected to structural analysis. The heparan sulphate proteoglycan from differentiated cells is larger and more homogeneous in size than the heparan sulphate proteoglycan from undifferentiated HT29 cells. No differences in protein core structure were observed when cells were labeled with [35S]methionine and the protein cores visualized by gel electrophoresis. Nevertheless, differences in glycosaminoglycan composition were found correlated with the degree of differentiation. The heparan sulphate chains from differentiated HT29MTX(-3) and HT29MTX(-6) cells have a higher sulphation degree than those from undifferentiated HT29 cells. The heparan sulphate from Caco2 cells is the most highly sulphated species. The differences are mainly attributed to O-sulphate groups. The increase in O-sulphation was more pronounced for D-glucosamine 6-O-sulphate than for L-iduronic acid 2-O-sulphate groups.
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PMID:Changes in glycosaminoglycan structure and composition of the main heparan sulphate proteoglycan from human colon carcinoma cells (perlecan) during cell differentiation. 966 Jan 93


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