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

Transforming growth factor (TGF)-beta 1 modulates the expression of extracellular matrix (ECM) glycoproteins, fibronectin and laminin and the adhesion of Moser colon cancer cells to these glycoproteins. Since adhesion can be altered through expression of cell-surface receptors, binding affinities of adhesion molecules for receptors, or both, we investigated the effect of TGF-beta 1 on the binding properties of fibronectin and laminin to their cell-surface receptors by saturation binding and Scatchard analyses using radiolabeled fibronectin and laminin. Fibronectin bound to its cell-surface receptor with high affinity (Kd = 1.25 x 10(-9) M), Moser cells had approximately 7.1 x 10(4) fibronectin-binding sites per cell. TGF-beta 1 treatment rapidly up-modulated the number of cell-surface fibronectin-binding sites by 1.9-fold. The binding affinity of fibronectin for the receptor, however, was not altered. Laminin was found to bind to a higher-affinity and a lower-affinity receptor. Moser cells expressed approximately 1.1 x 10(3) higher-affinity laminin-binding sites and approximately 3.1 x 10(4) lower-affinity-binding sites per cell. TGF-beta 1 rapidly increased the expression of the higher-affinity sites 3-fold and the lower-affinity sites 5-fold. The binding affinity of both the higher-affinity and lower-affinity laminin receptors increased 3-fold after 2 and 6 hr of TGF-beta 1 treatment respectively. Concurrent with receptor modulation, TGF-beta 1 induced the secretion of fibronectin and laminin from Moser cells. Northern hybridization analyses showed a concurrent stimulation of the expression of the mRNAs for ligands (fibronectin and laminin) and the mRNAs for the integrin species of the fibronectin and laminin receptors (alpha 5 and alpha 6 subunits). Thus the production of fibronectin and laminin and the expression of their receptors were tightly co-regulated by TGF-beta 1.
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PMID:Regulation of fibronectin and laminin receptor expression, fibronectin and laminin secretion in human colon cancer cells by transforming growth factor-beta 1. 819 84

Elevated expression of the c-myc oncogene is a frequent finding in tumors and cell lines derived from carcinomas of the colon and rectum. In a previous study we demonstrated that the differentiation agent sodium butyrate causes a rapid reduction in the expression of c-myc RNA in the rectal carcinoma cell line SW837. This effect was blocked by inhibitors of protein synthesis, suggesting that butyrate causes the induction of an activity that has a negative effect on c-myc expression. In the present work we demonstrate that the rapid decrease in the level of c-myc RNA, upon treatment of SW837 cells with 2 mM butyrate, is followed by a slower decrease in the level of p53 RNA and an increase in the RNA levels for fibronectin and a placental type alkaline phosphatase. Using in vitro elongation of nascent transcripts to measure transcription and actinomycin D chase experiments to measure RNA stability, we show that the reduction in expression of c-myc RNA is due to an increase in the block to transcriptional elongation, rather than a decrease in transcriptional initiation or an increase in degradation of the RNA. We conclude that sodium butyrate induces an activity that increases the transcriptional block in SW837 cells, and that regulation of transcriptional elongation is an important mechanism for regulating c-myc expression in this cell type. A shift in relative usage of the two major promoters in the c-myc gene accompanies the reduction in expression. The potential significance of this finding with respect to transcriptional elongation is discussed. Mutations in the exon 1/intron 1 boundary region of the c-myc gene cause an increase in transcriptional elongation in Burkitt lymphoma. We sequenced this region in a series of cell lines derived from colorectal carcinomas, all of which had an elevated level of c-myc expression, to determine if a similar mutational mechanism is at work in this disease. All of the lines examined had a normal c-myc DNA sequence, suggesting that the deregulation of c-myc expression in colon cancer is not due to a cis mutation in this region.
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PMID:Sodium butyrate causes an increase in the block to transcriptional elongation in the c-myc gene in SW837 rectal carcinoma cells. 837 1

The attachment of 7 human colon cancer lines transplantable into nude mice, and primary tumors and liver metastases from 30 patients with colon cancer to 4 extracellular matrix proteins (EMPs)--Matrigel, laminin, fibronectin, and type IV collagen--was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H (MTT) assay. Cancer cells from the 4 established tumor lines which produced experimental liver metastases in vivo showed significantly greater attachment to each EMP than those from the other 3 tumor lines which did not. Although there were no significant differences between attachment to EMPs of cancer cells from 15 clinical primary tumors with liver metastases and those without, attachment to each EMP of cells derived from liver metastases was significantly greater than that of the cells from the corresponding primary tumors in 8 cases for which liver metastases and primary tumors were examined simultaneously. Attachment to EMPs, which could be determined simply and rapidly using the MTT assay, is thus considered a significant factor in experimental and clinical liver metastases of human colon cancers.
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PMID:Significance of in vitro attachment of human colon cancers to extracellular matrix proteins in experimental and clinical liver metastases. 847 91

Alternative splicing of primary fibronectin (FN) mRNA results in the synthesis of different isoforms. ED-A+ and ED-B+ FN isoforms are absent from plasma FN and are representative of cellular FN. Their expression was studied in human and rat normal colon, in human colorectal carcinomas, and in transplanted tumors derived from a chemically-induced rat colon cancer. In normal colon, only the ED-A+ FN isoform was expressed as a thin deposit between crypt colonocytes and pericryptal myofibroblasts. Conversely, heavy ED-A+ FN deposits and lighter ED-B+ FN expression were found in the stroma of colorectal tumors in association with myofibroblasts surrounding tumor glands. Some colonic cancer cells also contained intracellular FN isoform granules and expressed FN mRNA. Tumor-associated myofibroblasts and some cancer cell lines were able to synthesize and deposit extracellular ED-A+ and ED-B+ FN in vitro. FN isoform deposition by tumor-associated myofibroblasts was not modulated by colon cancer cell-conditioned medium, but was strongly enhanced when myofibroblasts were cultured on colon cancer cell extracellular matrix or on laminin. These results show that the ED-A+ and ED-B+ FN isoforms were overexpressed in colorectal cancer. Cancer cells can deposit these FN isoforms directly and also stimulate their deposition by tumor-associated myofibroblasts.
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PMID:Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental colorectal cancer. Contribution of cancer cells and tumor-associated myofibroblasts. 857 20

Current data from in vitro and in vivo animal models indicate that fibronectin-binding integrin receptors expressed by colon cancer cells may regulate tumour growth. While individual members of the beta 1 subfamily of integrins have now been clearly identified in colorectal cancer, little information exists with respect to the alpha V subfamily. In the present study we show that alpha V can associate with multiple and different beta subunits capable of binding fibronectin in this tumour type. This is likely to have functional implications for growth and spread of colorectal cancer.
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PMID:Multiplicity of fibronectin-binding alpha V integrin receptors in colorectal cancer. 861 1

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

A simplified method to quantitatively analyze the migration and proliferation capacity of a colonic cancer cell line (SW837) in vitro was developed. The objective of this study was to evaluate the role of the extracellular matrix in colon cancer metastasis. We used this model to investigate the effects of the extracellular matrix components collagen type I and type IV, laminin, and fibronectin on the migration and the proliferation of cancer cells. Migration was fastest on laminin and slowest on collagen type I. Further, proliferation was highest on laminin of all extracellular matrices groups studied. Therefore, it is concluded that laminin had pronounced effects on migration and proliferation of SW837 cells. These findings suggest that the composition of the extracellular matrix plays an important role in the mechanism of metastasis of colon cancer cells.
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PMID:Role of extracellular matrix on colonic cancer cell migration and proliferation. 864 8

Binding of colon cancer to extracellular matrix (ECM) proteins and mesenchymal cells that comprise the basement membrane is important in migration and metastasis. This study defines the conditions and surface structures necessary for adhesion of HT-29 cells to ECM proteins and cell monolayers. Binding began within minutes and peaked by 1 hr, with 80-95% of HT-29 cells binding to the ECM proteins, collagen IV, laminin, fibronectin, and vitronectin and 40-75% binding to monolayers of fibroblasts, smooth muscle cells, and HT-29 cells. Treating mesenchymal cells with the fibrogenic cytokines, IL-1, IL-4, or TNF-alpha, which increase production of ECM proteins, did not alter binding of HT-29 cells to these monolayers. Attachment of HT-29 cells to cell monolayers was inhibited by cytochalasin D and sodium azide, but not cycloheximide or neuraminidase. Attachment to ECM proteins, in contrast, was unaffected by any of these metabolic inhibitors but required certain divalent cations (Mg2+ and Mn2+ but not Ca2+). Antibody to the integrin beta 1, chain (CD29) eliminated binding to collagen and laminin but not to fibronectin, fibroblasts, and HT-29 monolayers. Antibody to the vitronectin receptor inhibited binding to fibronectin. Antibodies to integrin alpha 1-alpha 6 chains had no effect on any adhesion event. Three colon cancer cell lines were tested for expression of VLA antigens: alpha 2 and alpha 3 were detected on all three, alpha 1 and alpha 6 were variably expressed, while alpha 4 and alpha 5 were absent. This study demonstrates that several mechanisms account for tumor cell attachment to substratum and cells.
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PMID:Mechanisms of colon cancer binding to substratum and cells. 876 78

Tumor spread may be favored by a reduced production and/or an enhanced degradation of extracellular matrix components (collagen, fibronectin, laminin). Most tumor cell behavior, from growth to spread, may be regulated by cytokines, the exact roles of which, however, are not yet fully understood. We here evaluate the effects of some cytokines (epidermal growth factor, transforming growth factor-beta 1, interleukin-1 alpha, and interleukin-1 beta) on both cell growth and the production of the aminoterminal peptide of type III procollagen, the urokinase plasminogen activator, and the plasminogen activator inhibitor-1 in neoplastic cell lines originating in the pancreas and colon. Cells were stimulated daily with the above cytokines and the aminoterminal peptide of type III procollagen, urokinase plasminogen activator, and plasminogen activator inhibitor-1 were measured in the conditioned media. Epidermal growth factor stimulated cell growth of both cell lines. Transforming growth factor-beta 1 counteracted cell proliferation and stimulated type III procollagen and plasminogen activator inhibitor-1 production only in the colon cancer cell line. Interleukin-1 alpha slightly stimulated cell growth, but inhibited plasminogen activator inhibitor-1 production in both cell lines; interleukin-1 beta did not affect cell growth, but stimulated plasminogen activator inhibitor-1 production by the colon cancer cell line. Our findings suggest that transforming growth factor-beta 1 and interleukin-1 beta may have an antidiffusive effect. These results confirm that cytokine-producing cells have a potential role in stimulating or counteracting tumor growth and spread and also confirm the pivotal role of host-tumor interactions in determining the outcome of a particular neoplasia.
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PMID:Cytokines may influence tumor growth and spread. An in vitro study in two human cancer cell lines. 900 14

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


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