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)

We investigated facilitation of invasion by growth factors and chemotactic factors in tumor cell lines, particularly hepatocellular carcinoma. Hepatoma cells (PLC/PRF/5 and Hep G2) showed strong chemotaxis toward their respective conditioned media while metastatic pancreatic cancer cells (SU.86.86) and colon cancer cells (LS 174T) did not migrate toward their respective conditioned media. Based on immunoblotting, PLC/PRF/5 cells secrete fibronectin (an extracellular matrix constituent), transforming growth factor-beta (TGFbeta; a growth factor), and cathepsin D (a protease). Fibronectin induced a migratory response in PLC/PRF/5 cells, and anti-fibronectin antibody abolished the migratory response of these cells to their conditioned medium. Anti-integrin-beta(1) antibody also impeded migration of these cells toward conditioned medium. Polyclonal anti-TGFbeta antibody and protease inhibitors (alpha(2)-macroglobulin and leupeptin) added to culture media-modulated secretion of fibronectin by PLC/PRF/5 cells. Although exogenous TGFbeta suppressed SU.86.86 cells, it enhanced PLC/PRF/5 cell adhesion to substrate, increasing viable cell numbers. These actions indicate that hepatocellular carcinoma may possess a forceful autocrine mechanism enabling cells to survive and proliferate under cirrhotic conditions.
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PMID:Secretion of extracellular matrix (fibronectin), growth factor (transforming growth factor beta) and protease (cathepsin D) by hepatoma cells. 1076 30

Transforming growth factor beta1 (TGFbeta) simultaneously induces the expression of fibronectin, fibronectin receptor, laminin, and laminin receptor (alpha6beta1 integrin) in the human colon cancer cell line Moser (Int J Cancer, 57:742, 1994). Induction of fibronectin and induction of fibronectin receptor by TGFB are tightly coupled, and disrupting fibronectin induction disrupts the induction of fibronectin receptor and cellular adhesion to fibronectin (J Cellular Physiol, 170:138, 1997). We recently demonstrated the efficacy of using antisense chain-specific laminin RNA expression vectors to disrupt the induction by TGFP of the multichain laminin molecule (J Cellular Physiol, 178:296, 1999). We now show in this report that Moser cells used alpha6 and beta1 integrins to adhere to laminin, and, as is the fibronectin and fibronectin receptor system, disrupting the induction by TGFbeta of the ligand laminin by the expression of antisense laminin A chain RNA disrupted the induction of 125I-laminin binding and cellular adhesion to laminin. Disrupting laminin induction also blocked the induction of alpha6 and beta1 integrin laminin receptor by TGFbeta. We conclude that disrupting the induction of the ligand laminin by TGFbeta disrupts TGFbeta-regulated laminin receptor function by suppressing the induction of alpha6 and beta1 integrins. Therefore, targeted disruption of the ligand laminin may be an effective means in disrupting the function of both the ligand and its receptor in cells that utilize the laminin and laminin receptor system in malignant cell behavior.
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PMID:Disruption of transforming growth factor beta-regulated laminin receptor function by expression of antisense laminin, a chain RNA in human colon cancer cells. 1114 13

Pancreatitis associated protein I is a secretory stress protein first characterized in pancreas during pancreatitis but also expressed in several tissues including hepatic, gastric, and colon cancer. Its concentration in serum can be significant. The relationship of pancreatitis associated protein I to skin cancers was investigated in normal melanocytes, melanoma tumors, and melanoma cell lines. None of them expressed pancreatitis associated protein I, even after stress induction. Adenovirus-mediated pancreatitis associated protein I expression, however, reduced cell adhesion to laminin-1 and fibronectin with a loss of integrin participation. Pancreatitis associated protein I expression stimulated haptotactic and directed migrations of some melanoma cells, but only directed migration was activated in normal melanocytes. Importantly, directed migration and spreading on fibronectin of the responsive melanoma cells were also enhanced when purified rat pancreatitis associated protein I was added to the culture medium of noninfected cells. This indicates that effects in infected cells were elicited by pancreatitis associated protein I after its secretion. Exogenous pancreatitis associated protein I can therefore modify the adhesion and motility of normal and transformed melanocytes, suggesting a potential interaction with melanoma invasivity.
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PMID:Pancreatitis associated protein I (PAP-I) alters adhesion and motility of human melanocytes and melanoma cells. 1123 17

A hallmark of transforming growth factorbeta (TGFbeta) action is the induction of the synthesis and secretion of extracellular-matrix adhesion molecules and induction of the cell-surface expression of integrin receptors for these molecules (termed extracellular-matrix remodeling). The signal pathways leading to extracellular-matrix remodeling and the significance of extracellular-matrix remodeling in TGFbeta function is not well-understood. In the epithelium-derived human colon cancer cell line Moser, TGFbeta induces extracellular-matrix remodeling in a protein kinase Calpha-dependent manner. In this study we showed that TGFbeta was a potent inducer of the homotypic cell-cell adhesion molecule E-cadherin and its undercoat-associated proteins, the catenins and dramatically increased the amount of E-cadherin/gamma-catenin complex formation. We found that the induction of E-cadherin and alpha- and beta-catenin by TGFbeta was also dependent on protein kinase Calpha, whereas the induction of gamma-catenin was independent of protein kinase Calpha but dependent on other protein kinase C isoforms. We also found that protein kinase Calpha-dependent induction of extracellular-matrix remodeling and subsequent cell-matrix interaction requiring both fibronectin and laminin were a prerequisite for the induction of E-cadherin (and alpha- and beta-catenin but not gamma-catenin) by TGFbeta. We therefore concluded that two signal pathways exist in TGFbeta-regulated expression of E-cadherin and the catenins. We also concluded that a functional significance of TGFbeta-induced extracellular matrix remodeling is the activation of signal transduction mechanisms through increased interaction between extracellular matrix fibronectin and laminin and their cell-surface integrin receptors, which lead to the induction of E-cadherin (and alpha- and beta-catenin).
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PMID:Requirement of protein kinase Calpha, extracellular matrix remodeling, and cell-matrix interaction for transforming growth factorbeta-regulated expression of E-cadherin and catenins. 1126 98

IGF-II is an autocrine growth factor for many colon cancer cells. This study aimed to determine the role of IGF-II in proliferation and adhesion of LIM 1215 colon cancer cells. RT-PCR demonstrated expression of IGF-I and IGF-II mRNA. Addition of IGF-I or -II increased monolayer proliferation in a dose-dependent manner. Although addition of IGFBP-6 had no effect on basal proliferation, coincubation of IGFBP-6 decreased IGF-II but not IGF-I-induced proliferation. Colony formation in agar was increased by IGF-II, an effect inhibited by coincubation with IGFBP-6. IGFBP-6 alone significantly decreased colony formation. Preincubation of cells with IGF-II increased adhesion to type IV collagen, fibronectin and laminin. IGFBP-6 had no effect on basal cell adhesion but completely inhibited the effects of IGF-II. LIM 1215 colon cancer cells are therefore IGF-responsive but IGF-II is not a major autocrine factor for these cells in monolayer, suggesting heterogeneity between colon carcinoma cell lines with respect to the role of the IGF system.
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PMID:Insulin-like growth factor (IGF)-binding protein-6 inhibits IGF-II-induced but not basal proliferation and adhesion of LIM 1215 colon cancer cells. 1130 78

Physical characteristics of surgical wounds and viable tumor cells shed may differ between open and laparoscopic procedures. Because environmental factors may vary between the laparoscopic milieu and that of open surgical procedures, we sought to characterize the effect of these factors on tumor cell adhesion, an early step in the process of wound implantation. Human SW620 colon cancer cells were placed in matrix-precoated dishes for 30 min at concentrations of 90,000-540,000 cells/well, at 25-37 degrees C, in the native state of the matrix proteins and after drying for 60 min, and in 0-10% serum. As increased pressure has previously been reported to stimulate colon cancer cell adhesion synergistically with serum, we then further partially characterized the serum components responsible for this potentiating effect. The number of adherent cells varied linearly with cells seeded. Adhesion was temperature-dependent, and also was dependent on the matrix conformation. Less adhesion occurred to dry matrix proteins. Serum dose-dependently potentiated SW620 pressure-stimulated adhesion, with a maximal increase in adhesion compared with ambient pressure conditions at 5% serum concentration. Heat inactivating the serum at 60 degrees C for 30 min ablated the effect. Filtration to remove molecules over 10 kDa produced no change in adhesion relative to ambient conditions, but filtration to 100 kDa preserved the serum effect. When the serum was passed over a gelatin-Sepharose column, which binds numerous proteins including fibronectin, the serum effect was lost. Addition of fibronectin to serum-free media did not reconstitute the effect. The environmental factors of warm temperature, moisture, and serum accumulation may contribute to increased colon cancer cell adhesion. However, the most important determinant of malignant adhesion to surgical wounds, laparoscopic or open, is likely to be the size of the tumor cell inoculum. Pressure stimulation of colon cancer cell adhesion is potentiated by heat-labile serum components of molecular weight 10-100 kDa which bind gelatin-Sepharose, and is not fibronectin alone. Irrigating serum from surgical wounds may decrease tumor implantation.
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PMID:Environmental factors of temperature, humidity, serum accumulation, and cell seeding increase colon cancer cell adhesion in vitro, with partial characterization of the serum component responsible for pressure-stimulated adhesion. 1139 24

Integrins play an important role in tumour progression by influencing cellular responses and matrix-dependent adhesion. However, the regulation of matrix-dependent adhesion assembly in epithelial cells is poorly understood. We have investigated the integrin and signalling requirements of cell-matrix adhesion assembly in colon carcinoma cells after plating on fibronectin. Adhesion assembly in these, and in the adenoma cells from which they were derived, was largely dependent on alpha v beta 6 integrin and required phosphorylation of FAK on tyrosine-397. The rate of fibronectin-induced adhesion assembly and the expression of both alpha v beta 6 integrin and FAK were increased during the adenoma-to-carcinoma transition. The matrix-dependent adhesion assembly process, particularly the final stages of complex protrusion that is required for optimal cell spreading, required the activity of extracellular signal-regulated kinase (ERK). Furthermore, phosphorylated ERK was targeted to newly forming cell--matrix adhesions in the carcinoma cells but not the adenoma cells, and inhibition of FAK--tyrosine-397 phosphorylation or MEK suppressed the appearance of phosphorylated ERK at peripheral sites. In addition, inhibition of MEK--ERK activation blocked the formation of peripheral actin microspikes that were necessary for the protrusive phase of cell-matrix adhesion assembly. Thus, MEK--ERK--dependent peripheral actin re-organization is required for the full development of integrin-induced adhesions and this pathway is stimulated in an in vitro model of colon cancer progression.
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PMID:The protrusive phase and full development of integrin-dependent adhesions in colon epithelial cells require FAK- and ERK-mediated actin spike formation: deregulation in cancer cells. 1149 15

The present experiments examined the potential ability of parathyroid hormone-related protein (PTHrP) to influence growth of the human colon cancer cell HT-29 and the ability of the cell to adhere to several extracellular matrix (ECM) proteins found in normal tissues. Addition of PTHrP analogs, PTHrP (1-34), PTHrP (67-86), or PTHrP (107-139), to HT-29 cells in culture did not influence cell growth or the adhesion of the cells to wells coated with fibronectin, laminin, or collagen type I. Likewise, in HT-29 cells induced to overexpress PTHrP by stable transfection with PTHrP cDNA, compared to vector-transfected control HT-29 cells, no effect on cell growth occurred. However, in the transfected cells, the increased production of PTHrP significantly enhanced cell adhesion to type I collagen but not to fibronectin or laminin. The results raise the possibility that PTHrP might play a role in colon tumor invasion and metastasis by influencing cell adhesion to specific extracellular matrix proteins.
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PMID:Parathyroid hormone-related protein overexpression in the human colon cancer cell line HT-29 enhances adhesion of the cells to collagen type I. 1149 75

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

The organ-specific metastasis characterizes several human cancers, including colon carcinoma, a disease that frequently involves metastases in the liver. The data on the molecular mechanisms of liver metastasis would therefore be highly useful for prognostic purposes. Although the upregulation/amplification of the hepatocyte growth factor (HGF) receptor, c-met, has been frequently observed in colon cancer metastasis, the actual functional significance of the feature in the liver metastatization is not yet known. We have used three human colon carcinoma cell lines (HT29, HT25 and WiDr), characterized by different liver metastatic potentials in SCID mice, to analyze the expression of c-met and the biological effects of HGF. We found that HGF induces scattering in in vitro liver-metastatic cell lines (HT25 and WiDr) only at doses which are non-mitogenic (1-20 ng/ml). Analysis of the c-met expression revealed that the metastatic cell lines express authentic c-met gene and protein material, unlike the non-metastatic HT29 cell line, which expresses only the c-terminal cytoplasmic domain of the c-met beta-chain. Interestingly, c-met was found to be localized in the substrate-attached peripheral membrane and partially colocalized with phosphotyrosine-proteins in the metastatic cells only when kept on fibronectin. On the other hand, we have analyzed 86 primary human colon cancers in Dukes' B (invasive but non-metastatic) and C (invasive and lymph node metastatic) stages. Western blotting of the proteins isolated from the tumor tissues and immunohistochemical control study on the paraffin samples of a third of these cases (25/86) all indicated a significant upregulation of the c-met protein in the Dukes' C tumor glands compared to the Dukes' B stages (P < 0.001 and P < 0.05, respectively). Since the two stages differ in the involvement of the regional lymph nodes but not in the invasion depth, the clinicopathological data and our experimental findings further support the notion that the c-met expression in human colon cancer can be considered as a marker of the metastatic potential due to its involvement in the generation of the motility signal.
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PMID:Experimental and clinicopathologic studies on the function of the HGF receptor in human colon cancer metastasis. 1182 67


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