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

Tumor invasion and metastasis involves the interaction between tumor cells and basement membrane, which is mediated in part by laminin receptors/laminin-binding proteins. We have reported that a 32-kDa laminin-binding protein (LBP-32) was overexpressed in colorectal cancer at the messenger RNA (mRNA) level and correlated with clinical staging. However, the function of this protein is not yet defined. In this study, we have analyzed the role of LBP-32 in tumor cell attachment and invasion through various basement membrane components. Blockade of LBP-32 synthesis with an anti-sense RNA was utilized in this study. The partial sequence (237 bp) of LBP-32 was inserted into the EMSV33 vector in the sense or antisense direction. Clone A, a poorly differentiated human colon carcinoma cell line, was transfected with EMSV33 alone (control), or EMSV33 with the insert in sense (LBP-S) or anti-sense (LBP-AS) direction using lipofectin. The cell adhesion assays (at 37 degrees C for 75 min) were performed using parental Clone A cells or the transfectants. Specific attachment to wells coated with laminin, fibronectin, or type IV collagen was evaluated. In vitro cell invasion assays were performed using the parental clone A cells and their transfectants to assess the passage through polycarbonate filters coated with matrigel, a reconstituted basement membrane. The results showed that (a) laminin and collagen IV (but not fibronectin) play a role in colon cancer cell attachment to substrata, and (b) anti-sense RNA of LBP-32 inhibits tumor cell attachment and invasiveness in vitro. These findings suggest a role for LBP-32 in colon cancer progression and metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-sense RNA of 32-kDa laminin-binding protein inhibits attachment and invasion of a human colon carcinoma cell line. 153 86

We have recently characterized the growth-inhibitory and cellular responses [carcinoembryonic antigen (CEA) secretion, protein secretion, protein expression, fibronectin and laminin synthesis] of the human colon carcinoma MOSER cell line to transforming growth factor-beta (TGF-beta) (Cancer Res., 47: 2950, 1987; 48: 4059, 1988). We have also recently isolated a subline (MOSER R2) from the parental MOSER cells which, unlike the parental line, is relatively resistant to the growth-inhibitory effect of TGF-beta (Biochem. Biophys. Res. Commun., 150: 711, 1988). We now report on the characterization of the cellular responses of this resistant MOSER R2 subline to TGF-beta and compare its responses to that of the highly growth-inhibition-sensitive MOSER cell line. In view of the reported relationship between CEA expression and differentiation in colon cancer and the ability of colon-derived substrata material to modulate the phenotypic properties of colon cancer cells, additional characterization and direct comparison of the effects of TGF-beta on the two cell lines were also performed with respect to (a) cellular expression of CEA and CEA cross-reactive glycoproteins; and (b) colon-derived substrata material. Unlike the growth-inhibition-sensitive MOSER cells, TGF-beta had no effects on fibronectin/laminin synthesis nor on the cellular morphology of the resistant MOSER R2 cells. TGF-beta was also unable to modulate protein secretion and deposition of substrata material by these cells. However, several other responses of the resistant cells to TGF-beta were found to be similar to that of the sensitive MOSER cells. These responses include: (a) a prolonged and stable secretion of CEA; (b) a prolonged and stable induction of elevated cellular expression of CEA and CEA cross-reactive glycoproteins; and (c) enhancement of the expression of three cellular proteins with molecular weights corresponding to 52,000, 48,000, and 42,000. We further report that the differences observed in the responses to TGF-beta in the two cell lines were not due to differences in TGF-beta binding or other receptor parameters such as the expression of distinct TGF-beta receptor subspecies.
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PMID:Diverse cellular responses elicited from human colon carcinoma cells by transforming growth factor-beta. 253 53

Collagen is the major constituent of the in vivo extracellular matrix environment and the ability of collagen substrates to support growth of cultured cells in vitro is well recognized. The aim of the present study was to examine in vitro proliferation and matrix-binding of cells obtained from a human colon fibroblast and four colon cancer cell lines cultured in a collagen matrix environment. In contrast to colon fibroblasts, colon cancer cell lines proliferated in this culture system and their proliferative capacities were dependent upon the collagen concentration and whether tumour cells were seeded on or in the collagen. Both laminin and fibronectin stimulated growth of one of the four colon cancer cell lines without an apparent increase in cell-matrix binding. The use of collagen matrices to culture tumour cells in vitro might facilitate identification of factors which regulate growth of an individual's colorectal cancer.
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PMID:Human colon cancer and fibroblast cell lines cultured in and on collagen gels. 273 Apr 61

The cell surfaces of human colon cancer cells before and after exposure to N,N-dimethylformamide (DMF) were probed using radioiodination and immunofluorescent labeling techniques. Growth of the human colon carcinoma cell line HCT MOSER in DMF-supplemented culture medium resulted in monolayer culture growth and marked cell morphology alterations consisting of cellular flattening and elongation. Accompanying the morphology alterations were distinct changes in the cell surface protein composition as determined by 125I labeling and electrophoresis. The cell surface changes associated with growth of HCT MOSER cells in the presence of DMF were dependent upon time of exposure to DMF and DMF concentration. Furthermore, removal of DMF-treated HCT MOSER cells from DMF-containing growth medium caused reversion of both cell morphology and cell surface composition to a state comparable to that of cells not exposed to DMF. The HCT MOSER cell surface alterations produced by DMF included a reduction of radioiodinated surface proteins with molecular weights of 87,000, 120,000, and 180,000 and an increase of a 125I-labeled surface protein with a molecular weight of 200,000-250,000. Appearance of a surface protein of approximately 200,000 molecular weight and assumption of a fibroblast-like morphology by DMF-treated HCT MOSER cells suggested that this approximately 200,000 molecular weight material might be fibronectin. Immunofluorescent labeling with anti-human fibronectin showed that HCT MOSER cells grown in DMF did manifest an anti-fibronectin immunoreactive material that was only transiently associated with the cell surface before being released. DMF-treated HCT MOSER cultures continued to express surface carcinoembryonic antigen, indicating that the presence of material immunoreactive with anti-human fibronectin was not secondary to proliferation of a contaminating fibroblast population. The response of HCT MOSER cells to DMF paralleled in many ways that previously reported for methylcholanthrene-transformed AKR-2B (AKR-MCA) fibroblasts. However, unlike AKR-MCA cells, HCT MOSER cells did not exhibit an increase in 125I incorporation per microgram DNA as a function of time of exposure to DMF, which suggests that the surface protein with a molecular weight of approximately 200,000 induced by DMF was not retained on the cell surface.
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PMID:N,N-dimethylformamide-induced synthesis of an anti-fibronectin reactive protein in cultured human colon carcinoma cells. 375 77

Monoclonal antibody B72.3 was generated using a membrane-enriched fraction of cells from a mammary carcinoma metastasis and has been shown previously to have a high degree of selective reactivity for human breast and colon carcinoma versus normal adult tissues. The reactive antigen has been shown to be a high-molecular-weight glycoprotein complex of approximately 220,000 to 400,000 and is termed tumor-associated glycoprotein 72 (TAG-72). We report here a dichotomy in the expression of TAG-72 in carcinoma biopsy material versus carcinoma cell lines. While 44% (25 of 56) of human breast carcinoma and 80% (16 of 20) of colon carcinoma biopsies express TAG-72 as assayed by radioimmunoassay or immunohistochemistry, only one of 25 breast cancer cell lines [MCF-7 (one variant)] and one of 18 colon cancer cell lines (LS-174T) express this antigen. Furthermore, TAG-72 expression in these two cell lines was shown to be a property of a low percentage of cells within each culture. Attempts to enhance TAG-72 expression in LS-174T cells by propagation on extracellular matrix proteins, such as collagen, laminin, and fibronectin, or in serum-containing or serum-free, hormone-supplemented medium proved unsuccessful. A pronounced increase in TAG-72 expression was observed, however, when the LS-174T cells were grown under culture conditions which promote three-dimensional growth. LS-174T cells grown in spheroid or suspension cultures demonstrated a 2- to 7-fold increase in TAG-72 antigen expression, while those grown on agar plugs demonstrated a 10-fold increase. When the LS-174T cell line was injected into athymic mice to generate tumors, the level of TAG-72 antigen increased over 100-fold, to levels comparable to those seen in the metastatic tumor masses from patients. Thus, spatial configuration of carcinoma cell populations is shown to influence the expression of a tumor-associated antigen and the subsequent surface binding of monoclonal antibody B72.3. The implications of these findings in the potential utility of monoclonal antibodies for the in vivo detection and destruction of carcinoma masses are discussed.
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PMID:Influence of spatial configuration of carcinoma cell populations on the expression of a tumor-associated glycoprotein. 388 Nov 73

Plasma fibronectin was measured in patients with breast cancer, colon cancer, and acute leukemia. In the patients with solid tumors, mean levels were significantly elevated above the mean level of age- and sex-matched normals whether the disease was thought to be metastatic or not (P less than 0.001). It did not make a difference whether the determinations were done prior to or during chemotherapy. Fibronectin was measured serially in eight hospitalized patients with leukemia during intensive induction chemotherapy. Normal concentrations were found prior to therapy. However, fibronectin concentration fell on the day following chemotherapy in nine of 12 episodes (P less than 0.05), and during sepsis in 13 of 13 episodes (P less than 0.001). Thus, the concentration was influenced by at least two factors: recent chemotherapy and sepsis. Because fibronectin concentration is sensitive to clinical events other than the status of the malignancy, it seems unsuitable as a tumor marker, at least as a single isolated measurement.
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PMID:Fibronectin concentration in plasma of patients with breast cancer, colon cancer, and acute leukemia. 657 2

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

In this study we have determined the effects of the n-6 essential fatty acid gamma-linolenic acid (GLA) on the motility and invasive/metastatic nature of the human colon cancer cell lines HT115, HT29 and HRT18. Cell motility was induced by hepatocyte growth factor/scatter factor (HGF/SF) and measured by both colony scattering and dissociation from carrier beads. Invasiveness was measured in vitro by cellular invasion into extracellular matrix. At concentrations up to 100 microM (which had no effect on cell growth over the duration of the experiments) both cell motility and invasion induced by HGF/SF were markedly reduced by GLA and its lithium salt. The attachment of these cells to the extracellular matrix components (Matrigel and fibronectin) was also inhibited. There were also changes in the cell-surface E-cadherin, but not fibronectin receptor at similar concentrations. It is concluded that n-6 essential fatty acids have the ability to inhibit both motility and invasiveness of human colon cancer cells, perhaps by modifying cell-surface adhesion molecules.
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PMID:Inhibition of hepatocyte growth factor-induced motility and in vitro invasion of human colon cancer cells by gamma-linolenic acid. 771 Sep 39

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

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


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