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

An epithelial cell line, LS123, was established in 1974 from the second in a series of three primary colonic tumors resected from a Caucasian female. The cell line is aneuploid, releases low concentrations of carcinoembryonic antigen (CEA), fails to grow progressively in nude mice, and forms colonies only in enriched semisolid medium developed for tumor stem cells. LS123 cells grow on confluent cell monolayers and in either low serum or serum-free medium. In the chick embryonic skin assay, LS123 cells grew as a well-differentiated abnormal colonic epithelium with little mitotic activity but with some indication of invasion. On floating collagen gels LS123 cells formed a one to three-cell-layer-thick undifferentiated epithelial sheet. The apparent low invasiveness of the cells of this line is supported by the patient's history of three primary colon tumors without systemic metastases during the past 30 yr. Therefore, although LS123 cells possess several properties associated with neoplasia, they have little invasive potential. Thus, LS123 cells may represent an important model for the study of human colon cancer.
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PMID:Characterization of a human colonic adenocarcinoma cell line, LS123. 682

Staurosporin, a broad-spectrum kinase inhibitor, induced cell spreading in a human colon cancer cell line, Colo 201. On collagen and laminin, cell spreading was induced in more than 90% of the cells and was dependent on very late activation antigen-3, as shown by an antibody inhibition assay. Cell spreading required divalent cations and showed the order of preference Mn2+ > Mg2+ > Ca2+. On fibronectin, only about 30% of the cells were observed to spread, and spreading occurred via a non-integrin, RGD-independent pathway. Staurosporin-induced spreading was inhibited by treatment with tyrosine kinase inhibitors herbimycin A and methyl 2,5-dihydroxycinnamate. Despite the presence of staurosporin, seven proteins (220, 175, 150, 98, 62, 58, and 45 kDa) showed increased levels of tyrosine phosphorylation in association with cell adhesion. Two of these (58 and 220 kDa) were identified by immunoprecipitation as Src product and tensin, respectively. Flow cytometric analysis showed that the Colo 201 cells expressed the alpha 2, alpha 3, alpha 6, and beta 1 chains of integrin, but expression of these chains was not influenced by staurosporin. Immunofluorescence microscopy revealed that the alpha 3 chain, diffusely expressed on the cell surface in the absence of staurosporin, was concentrated at focal adhesion plaques after staurosporin treatment. Neither alpha 2 nor alpha 6 was focalized by the treatment.
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PMID:Cell spreading in Colo 201 by staurosporin is alpha 3 beta 1 integrin-mediated with tyrosine phosphorylation of Src and tensin. 753 Jul 22

Epidemiologic studies have linked diets high in animal fat with colon carcinogenesis. A number of animal tumor models have shown that diets rich in omega-3 fatty acids inhibit colon carcinogenesis while diets rich in omega-6 fatty acids promote tumor growth. This study examines whether modification of the membrane fatty acid composition of both moderately (CX-1) and poorly differentiated (MIP-101 and Clone A) human colorectal carcinoma cells alters their interaction with Kupffer cells and extracellular matrix proteins (collagen type IV, fibronectin and laminin). The cells were treated with 15-16 micrograms/ml of docosahexanoic acid (22:6, omega 3) or linoleic acid (18:2,omega 6). Gas chromatography showed significant alterations in the membrane fatty acid composition of the human colorectal cancer cell lines. Binding assays were performed by measuring adherence of 51Cr-labelled tumor cells to Kupffer cell monolayers or to immobilized proteins. Omega-3 treatment significantly decreased the Kupffer cell binding of only the CX-1 line while omega-6 treatment decreased binding of all three cell lines. In contrast both omega-3 and omega-6 treatment of MIP-101 cells decreased binding to the extracellular matrix proteins with the omega-6 effect being more pronounced. These results indicate that the binding characteristics of the colon cancer cells to both Kupffer cells and extracellular matrix proteins may be determined in part by the membrane fatty acid composition. Decreased adherence to extracellular matrix proteins may lead to increased cell motility and invasiveness. Since Kupffer cell binding precedes tumor cell phagocytosis and killing, decreased binding may improve tumor cell survival.
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PMID:Effect of membrane free fatty acid alterations on the adhesion of human colorectal carcinoma cells to liver macrophages and extracellular matrix proteins. 788 22

The effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the growth characteristics of the colon cancer cell line HT-29 M6 were studied. TPA induced the scattering of proliferative HT-29 M6 cells: in the presence of the phorbol ester, HT-29 M6 colonies scattered and the cells acquired a flatter aspect with diminished cell-cell contacts. This effect of TPA required a persistent activation of PK-C and was accompanied by a slight decrease (30%) in the growth rate. Modifications by TPA of two scattering associated properties of these cells were also detected: TPA decreased cell-to-cell aggregation and enhanced the cellular attachment to matrix substrata (collagen, laminin). The decrease in cell-to-cell adhesion was correlated with a loss of cellular E-cadherin as evidenced by immunofluorescence or immunoblotting with a specific monoclonal antibody. Cell scattering was dependent on the extracellular concentration of Ca2+; an increase from 1.6 to 10 mM in the concentration of this ion completely blocked the morphological effects of TPA as well as its action on cell aggregation. This high concentration of Ca2+ also prevented the down modulation of E-cadherin as determined by immunofluorescence. However, the TPA-induced increase in cell attachment to the matrix was not affected by high calcium. These findings support the importance of altered cell-cell adhesion in the process of scattering and provide a good system for the study of down modulation of E-cadherin, a protein involved in the control of cell growth, differentiation and invasion of epithelial cells.
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PMID:Phorbol ester-induced scattering of HT-29 human intestinal cancer cells is associated with down-modulation of E-cadherin. 828 58

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

The gene expression of two type IV collagen-degrading enzymes (72-kd and 92-kd type IV collagenases) was investigated in human colon adenocarcinomas by in situ hybridization. In all cases (18 out of 18), messenger RNA for the 72-kd type IV collagenase was present and located in numerous fibroblasts in the stroma surrounding the invasive cancer tissue. In normal-appearing colonic mucosa distant from the cancer tissue, either no expression or only very weak expression of this enzyme was detected. Also the 92-kd type IV collagenase was found in all samples investigated (10 out of 10), exclusively expressed by tissue macrophages. A very strong hybridization signal for messenger RNA for the 92-kd enzyme was found in a subpopulation of tissue macrophages surrounding invading malignant epithelium. In normal-appearing colon tissue, a markedly weaker hybridization signal was observed in macrophages contained in Peyer's patches. No hybridization signals for either of the two type IV collagenases were detected in cancer cells. Together with previous findings on expression of components of the plasminogen activation system, these results indicate that several nonepithelial cell types in the tumor stroma are involved in production of factors involved in extracellular proteolysis during colon cancer invasion.
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PMID:Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer. 843 36

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

A hepatocyte-derived cell line designated MLE-15A2 was established from a primary culture of mouse hepatocytes. The MLE-15A2 cells appeared to retain the basic nature of hepatocytes in that they showed morphology of an epithelial cell type and secreted albumin into the culture medium. These cells were grown on collagen-coated plates and could be easily expanded to a large-scale culture. Therefore, MLE-15A2 cells may provide a more useful model for studying liver microenvironments than primary cultures of hepatocytes. We found that conditioned media from MLE-15A2 cells, as well as from primary cultures of hepatocytes, promoted the proliferation of highly liver-colonizing colon 26 NL-17 cells better than the poorly liver-colonizing colon 26 NL-4 cells. Moreover, the conditioned media stimulated the growth of some human colon cancer cell lines. These results indicate that MLE-15A2 cells secrete growth factors that selectively stimulate certain tumor cell types. Hepatocyte-derived growth factors may regulate selective survival and colonization of tumor cells in the process of liver metastasis. The growth-promoting activity was unaffected by dialysis, was stable at 80 degrees C for 30 minutes and was bound to a heparin-Sepharose column. The major activity was eluted from the column with 0.7-0.75 M NaCl, and some minor activities eluted with lower concentrations of NaCl. These results suggest that the active components are heterogeneous heparin-binding proteins with lower affinity to heparin than platelet-derived and fibroblast growth factors.
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PMID:Establishment of a hepatocyte cell line producing growth-promoting factors for liver-colonizing tumor cells. 860 63

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


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