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)

MUC1 mucin is expressed in a wide variety of tumors and is considered to function as an anti-adhesion molecule which inhibits cell-to-cell interactions. To reveal the biological significance of this activity in tumor cells, MUC1 cDNA was transfected into EJNIH3T3 cells and human colon cancer cell lines, CHCY1 and DLD1. The in vivo growth rate of MUC1+ (MUC1-transfected) EJNIH3T3, CHCY1 and DLD1 cells in SCID mice was clearly lower than that of MUC1- (mock transfectant) cells. Several in vitro experiments using MUC1+ EJNIH3T3 cells were performed to analyze the mechanisms for the decreased in vivo tumor growth. It was found that (i) the in vitro growth rate of MUC1+ EJNIH3T3 cells was also decreased compared to that of MUC1- cells, (ii)the DNA synthesis of MUC1+ EJNIH3T3 cells after stimulation with either growth factor (fetal calf serum or bombesin) or extracellular matrix (collagen or fibronectin) was lower than that of MUC1- cells, and (iii) MUC1+ EJNIH3T3 cells grew more slowly than MUC1- cells on both collagen- and fibronectin-coated dishes. These data suggest that MUC1 mucin may regulate tumor cell growth through inhibition of cell-to-cell, growth factor-to-receptor and cell-to-matrix interactions.
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PMID:Effect of MUC1 mucin, an anti-adhesion molecule, on tumor cell growth. 864 88

Mucinous colorectal cancers have a poorer prognosis than colorectal cancers which produce a low amount of mucin, but the exact mechanism is not well understood. The present study was undertaken to elucidate the possible mechanisms of invasion and metastasis of colon cancer cells producing high levels of mucin using mucin glycosylation inhibitor, benzyl-alpha-N-acetylgalactosamine. The binding activity of treated HM7 cells to endothelial leukocyte adhesion molecule (ELAM-1) was significantly decreased and fixed cell binding of MoAb SNH-3 and 19-9 (specific for sialyl Le(x) and sialyl Le(a), respectively) was also significantly decreased. Metalloproteinase activity in conditioned medium and invasion of matrigel-coated porous filters by treated HM7 cells were decreased. However, there was no difference between control and treated HM7 cells in terms of matrix protein binding. These results suggest that O-glycosylated mucin is important in the invasive and metastatic properties of HM7 human colon cancer cells.
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PMID:Effect of O-glycosylated mucin on invasion and metastasis of HM7 human colon cancer cells. 865 7

Human carcinoembryonic antigen (CEA) is overexpressed in a wide variety of epithelial malignancies including colon cancer. CEA can function in vitro as a homotypic intercellular adhesion molecule and can block the terminal differentiation of rodent myoblasts, thus raising the possibility that deregulated expression of CEA might directly contribute to malignant progression. To address this question, the expression pattern and cell-surface levels of CEA were studied during malignant transformation of the colonic epithelium in sporadic and familial adenomatous polyposis-related neoplasms. The level of immunohistochemically detected CEA was higher in 30% to 62% of microadenomas and small adenomas from familial adenomatous polyposis patients compared with adjacent normal mucosa, and this proportion was positively correlated with lesion size and degree of dysplasia. Cytofluorometric analysis of highly purified single epithelial cell suspensions from freshly excised carcinomas versus adjacent normal tissue demonstrated up to a 20-fold increase of mean cell-surface CEA in a group of colon carcinomas representative of the overall majority of such tumors--from Dukes' stages A to D and ranging mainly from well to moderately differentiated, the degree of overproduction was inversely correlated with tumor differentiation and directly correlated with stage. A marked tendency toward nonpolarized versus apical cell-surface expression with progression was also noted. Nonspecific cross-reacting antigen (NCA), a CEA family member, is also a homotypic adhesion molecule and blocks terminal myogenic differentiation, whereas biliary glycoprotein is a CEA family adhesion molecule that does not. Cell-surface NCA showed even greater overexpression (up to 70-told) in dedifferentiated tumors, whereas total-cell biliary glycoprotein showed approximately 2-fold lower levels than was normal in more differentiated tumors and approximately 2-fold higher levels than in further progressed tumors. These results therefore support the suggestion that CEA and NCA can directly contribute to colon carcinogenesis by inhibiting colonocyte differentiation.
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PMID:Cell-surface levels of human carcinoembryonic antigen are inversely correlated with colonocyte differentiation in colon carcinogenesis. 916 89

The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been described in gastric cancer and preneoplastic lesions. The APC locus has been recently related to a cell surface adhesion molecule and its alteration may favour metastatic dissemination. LOH at 5q21 has been associated with poor prognosis in other tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic markers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia were also added to the study. LOH was determined in 84% of the informative cases of GC, affecting both early and advanced stages of disease. Genomic instability was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intestinal carcinoma without evidence of recurrence after a 36 month follow-up period (the mean survival rate in our series was 28.3% at 36 months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found.
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PMID:LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications. 918 90

Alterations in several classes of adhesion molecule have been implicated in the progression of colorectal cancer. Cell adhesion regulator (CAR) has been identified as a regulator molecule of integrin-dependent cell adhesion. We have explored the possible involvement of the CAR gene in colorectal cancer. Reverse transcription-PCR revealed that CAR expression was detected in normal colonic cells, whereas it was decreased or undetectable in 6 of 13 (46.2%) human colon cancer cell lines. Adhesion of HT-29 cells to extracellular matrix components was up-regulated by the introduction of CAR. CAR-transfected HT-29 cells showed a significantly reduced spontaneous metastatic potential in nude mice. In 14 of 30 cases (46.7%), CAR expression in cancer was less than one-tenth of that in matched noncancerous tissue. The tumor: normal ratio of CAR expression was significantly lower in patients with lymph node metastases than in those without (p < 0.01) and in patients with distant metastases than in those without (p < 0.05). CAR expression was significantly lower in more advanced Dukes' stage tumors (p < 0.05). Our results suggest that down-regulation of CAR expression may play an important role in the progression and metastasis of colorectal cancer.
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PMID:[Regulation of integrin function in the metastasis of colorectal cancer]. 974 20

Intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and the lymphocyte function-associated antigen (LFA-1) are cell adhesion molecules thought to play an important role in the complex process of airway inflammation and tumor cell growth. The aim of this study was to examine the distribution of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of lung and in major cellular compartments of non-neoplastic lung tissue. We examined cellular compartments in tissue from five bronchoalveolar carcinomas, three acinar adenocarcinomas, and one colon cancer metastatic to the lung. The compartments in neoplasms included the tumor cells proper, endothelial cells within the tumor vasculature, tumor stromal cells, and tumor-infiltrating lymphocytes. The compartments in non-neoplastic lung tissue included lung endothelial cells, pulmonary lymphocytes, interstitial fibroblasts, Type II alveolar pneumocytes, and bronchial epithelial cells. ICAM-1 was expressed in tumor cells from all of the nine adenocarcinomas. In contrast, VCAM-1 expression was not identified in tumor cells from any of the nine adenocarcinomas. ICAM-1 was expressed in all cellular compartments of the non-neoplastic lung tissue, whereas VCAM-1 was expressed only in pulmonary lymphocytes and interstitial fibroblastic cells. LFA-1 was uniformly expressed in tumor-infiltrating lymphocytes from each of the nine tumors and all of the lymphocytes in non-neoplastic lung tissue. This study showed major differences in the expression of ICAM-1 and VCAM-1 in tumor cells from pulmonary adenocarcinoma and also provided evidence for a wider distribution of ICAM-1, compared with VCAM-1, in non-neoplastic cellular compartments of the lung. ICAM-1 expression was particularly noticeable in bronchial and alveolar epithelial cells. Upregulation of ICAM-1 in pulmonary adenocarcinoma might foster binding by LFA-1-bearing lymphocytes, with a possible impact on the vulnerability of tumor cells to host defense mechanisms.
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PMID:Expression of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of the lung with observations on the expression of these adhesion molecules in non-neoplastic lung tissue. 987 50

beta-Catenin mediates the interaction of E-cadherin with alpha-catenin and the actin cytoskeleton. Recent evidence indicates that when the tumor suppressor gene APC is inactivated, beta-catenin can translocate to the nucleus, where it acts as a transcriptional regulator. Because APC is inactivated in most colorectal cancers, beta-catenin nuclear localization would be expected in these tumors. In a study of adhesion molecule expression in frozen colorectal cancer tissues, we were surprised by failure to detect nuclear beta-catenin. Here we compared the reactivity of an anti-beta-catenin monoclonal antibody with 11 colorectal cancers using immunohistochemistry on sections of frozen or paraffin-embedded samples. beta-Catenin was never detected in the nuclei of normal or tumor cells in frozen tissue sections. By contrast, in 8/11 cases it was detected in the nuclei of tumor cells but not of normal cells in paraffin-embedded tissue sections. These results were confirmed with an independent rabbit polyclonal anti-beta-catenin serum. We also examined beta-catenin distribution in SW480 colon cancer cells, in which its nuclear accumulation has been reported. As in tissues, nuclear beta-catenin was detected in paraffin-embedded but not in frozen samples. These findings are relevant because of the increasing interest in the study of beta-catenin in tumors, based on its dual role in cell adhesion and transcriptional regulation.
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PMID:Nuclear beta-catenin in colorectal tumors: to freeze or not to freeze? Colon Cancer Team at IMAS. 1042 93

We investigated the role of tumor cell-derived GM-CSF in recruitment and tumoricidal activation of tissue macrophages. Transfection of the murine GM-CSF gene into KM12SM human colon cancer cells decreased the tumorigenicity of transfected cells and nontransfected bystander colon cancer cells in nude mice. Sequential tissue sections from sites injected with high GM-CSF-producing tumor cells (but not from nontransfected or low GM-CSF-producing cells) demonstrated a dense infiltration of polymorphonuclear cells (PMN), followed by infiltration of macrophages, which correlated with expression of the macrophage-inflammatory protein-1alpha and the monocyte chemoattractant protein-1 (MCP-1) in mouse PMN and macrophages. GM-CSF-producing KM12SM cells were highly sensitive to lysis by mouse macrophages and also increased macrophage-mediated lysis of bystander nontransfected KM12SM cells. The incubation of macrophages with GM-CSF induced expression of the CD11b surface adhesion molecule, which was associated with increased attachment to tumor cells. All KM12SM cells were sensitive to macrophage-mediated lysis in the presence of rGM-CSF and recombinant MCP-1. Collectively, the results demonstrate that tumor cell-derived GM-CSF stimulates PMN and macrophages to secrete macrophage-inflammatory protein-1alpha and MCP-1, which triggers recruitment of mononuclear cells, induces expression of adhesion molecules on macrophages, and enhances contact-dependent cytolysis of tumor cells.
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PMID:Induction of chemokine secretion and enhancement of contact-dependent macrophage cytotoxicity by engineered expression of granulocyte-macrophage colony-stimulating factor in human colon cancer cells. 1067 14

We have previously reported that down-regulation of Cdx1 and Cdx2 mRNA expression is associated with colon carcinogenesis, and that coordinated reexpression of these genes in the HT29 colon cancer-derived cell line leads to a reduced malignant phenotype. Here we show that restoring Cdx1 and Cdx2 expression in HT29 cells enhanced the antigen presentation system, as reflected by a strong induction of the concentration of HLA-I molecules at the cell surface, resulting from increased expression of the HLA-I mRNA. Expression of the LMP2 proteasomal protein was also strongly induced by Cdx1 and Cdx2 at the transcriptional level, whereas TAP1 expression which is under the control of the same bidirectional promoter as LMP2 remained unchanged. Furthermore, expression of the adhesion molecule ICAM-1, which works in concert with HLA-I, and of the cell death promoter Fas was also increased upon Cdx1 and Cdx2 expression. Taken together, these results suggest that loss of Cdx1 and Cdx2 expression during colorectal carcinogenesis could favor the escape of tumor cells from the immune system. In conclusion, restoration of Cdx1 and Cdx2 expression should be considered in immunotherapeutic strategies for colorectal cancer.
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PMID:Overexpression of Cdx1 and Cdx2 homeogenes enhances expression of the HLA-I in HT-29 cells. 1096 50

Transforming growth factor beta1 (TGFbeta) inhibits cellular proliferation, promotes differentiation, and stimulates the expression and secretion of the extracellular matrix adhesion molecules fibronectin and laminin and the colon-associated intercellular adhesion molecule carcinoembryonic antigen. This is collectively called the TGFbeta-mediated adhesion response and occurs in the human colon cancer cell line Moser while the cell line KM12SM is relatively unresponsive to TGFbeta. We have previously shown that TGFbeta rapidly stimulates protein kinase C (PKC) phosphotransferase activity in the Moser cells and that the induction of the adhesion response (but not antiproliferation) by TGFbeta is dependent on PKC. Because resistance to growth factors may be due to translational suppression and the translation initiation factor eIF-4E may alleviate translational suppression, we determined the effect of eIF-4E expression on the responses of Moser and KM12SM cells to TGFbeta. Ectopic expression of eIF-4E in the TGFbeta-responsive Moser cells enhanced the activation of PKC by TGFbeta and the induction of the adhesion response, especially the secretion of adhesion molecules, but not the antiproliferative response. Ectopic expression of eIF-4E in the TGFbeta-resistant KM12SM cells increased TGFbeta stimulation of PKC and the TGFbeta-mediated adhesion response (but not antiproliferation). The secretion of adhesion molecules was significantly increased by TGFbeta. These results showed in these cells that eIF-4E promotes TGFbeta-regulated adhesion but not antiproliferation in a PKC-dependent manner.
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PMID:Ectopic expression of eIF-4E in human colon cancer cells promotes the stimulation of adhesion molecules by transforming growth factorbeta. 1177 28


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