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

Matrix metalloproteinases (MMPs) such as gelatinases are believed to play an important role in invasion and metastasis of cancer. In this study we investigated the possible role of MMP-2 and MMP-9 in an experimental model of colon cancer metastasis in rat liver. We demonstrated with gelatin zymography that the tumors contained MMP-2 and MMP-9, but only MMP-2 was present in the active form. Immunolocalization of MMP-2 showed that the protein was localized at basement membranes of colon cancer cells and in intratumor stroma, associated with extracellular matrix (ECM) components. However, zymography and immunohistochemistry (IHC) do not provide information on the localization of MMP activity. Therefore, we developed an in situ zymography technique using the quenched fluorogenic substrate DQ-gelatin in unfixed cryostat sections. The application of DQ-gelatin in combination with a gelled medium allows precise localization of gelatinolytic activity. Fluorescence due to gelatinolytic activity was found in the ECM of tumors and was localized similarly to both MMP-2 protein and collagen type IV, its natural substrate. The localization of MMP-2 activity and collagen type IV at similar sites suggests a role of MMP-2 in remodeling of ECM of stroma in colon cancer metastases in rat liver.
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PMID:In situ localization of gelatinolytic activity in the extracellular matrix of metastases of colon cancer in rat liver using quenched fluorogenic DQ-gelatin. 1275 93

In an effort to identify novel genes relevant to tumor angiogenesis, we compared the genes expressed in a matched pair composed of vascularized breast tumor and its adjacent normal tissue obtained from the same cancer patient. Using differential display, we identified a cDNA fragment that was reproducibly upregulated in vascularized breast tumor. Up-regulation of this gene fragment in vascularized breast tumor was further verified by semi-quantitative PCR on the same RNA pair using gene-specific primers. The cDNA encoding the full-length ORF of that gene was then cloned by both 3' and 5' RACE. Sequence analysis showed that this gene encodes an ORF of 1353 bp having a hydrophobic N-terminal signal sequence and a cleavage site. We named this novel gene BNF-1 (breast tumor novel factor 1). The mature protein of this gene contains cysteine-rich repeats that are a specific feature of several extracellular matrix proteins including thrombospondin-1, thrombospondin-2, pro-collagen type 1, and von Willebrand Factor 1. PCR analysis of BNF-1 expression in a variety of human adult normal tissues revealed that BNF-1 is expressed predominantly in liver, heart, prostate, testis, and ovary. To further study the expression pattern of this novel gene in tumor tissues, we extended our analysis to additional matched pairs of tumor tissues obtained from breast, lung, and colon cancer patients. We show here that BNF-1 is over-expressed not only in breast tumors but also in lung and colon tumors.
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PMID:BNF-1, a novel gene encoding a putative extracellular matrix protein, is overexpressed in tumor tissues. 1285 44

Cell-cell and extracellular matrix adhesions play important roles in the progression of cancer. We investigated the involvement of the inflammatory mediator leukotriene D4 (LTD4) in the regulation of cell-matrix adhesion of colon cancer (Caco-2) cells. We observed that LTD4 acted via its CysLT1 receptor in these cells to induce increased adhesion to collagen I. LTD4 also enhanced the activation and expression of alpha2beta1-integrins on the cell surface, which we found to be responsible for mediating the increased adhesion to collagen I. LTD4 simultaneously augmented expression of the prostaglandin-generating enzyme cyclooxygenase-2 (COX-2) and increased prostaglandin E2 (PGE2) production in Caco-2 cells. The adhesive capacity of the Caco-2 cells was reduced by specific inhibition of COX-2 and was subsequently restored by PGE2, but not by LTD4. A selective PGE2 receptor antagonist abolished the increased adhesion and the augmented alpha2beta1-integrin expression induced by both PGE2 and LTD4. Summarizing, the inflammatory mediator LTD4 regulates the adhesive properties and migration of the Caco-2 cell line by upregulating COX-2 and stimulating PGE2-induced expression of alpha2beta1-integrins. This suggests that inflammatory mediators such as LTD4 can be involved in the dissemination and survival of colon cancer cells.
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PMID:Leukotriene D4-induced adhesion of Caco-2 cells is mediated by prostaglandin E2 and upregulation of alpha2beta1-integrin. 1449 35

In colon cancer, enteric bacteria and dietary factors are major determinants of the microenvironment but their effect on cellular invasion is not known. We therefore incubated human HCT-8/E11 colon cancer cells with bacteria or bacterial conditioned medium on top of collagen type I gels. Listeria monocytogenes stimulate cellular invasion through the formation of a soluble motility-promoting factor, identified as a 13mer beta-casein-derived peptide (HKEMPFPKYPVEP). The peptide is formed through the combined action of Mpl, a Listeria thermolysin-like metalloprotease, and a collagen-associated trypsin-like serine protease. The 13mer peptide was also formed by tumour biopsies isolated from colon cancer patients and incubated with a beta-casein source. The pro- invasive 13mer peptide-signalling pathway implicates activation of Cdc42 and inactivation of RhoA, linked to each other through the serine/threonine p21- activated kinase 1. Since both changes are necessary but not sufficient, another pathway might branch upstream of Cdc42 at phosphatidylinositol 3-kinase. Delta opioid receptor (deltaOR) is a candidate receptor for the 13mer peptide since naloxone, an deltaOR antagonist, blocks both deltaOR serine phosphorylation and 13mer peptide-mediated invasion.
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PMID:Beta-casein-derived peptides, produced by bacteria, stimulate cancer cell invasion and motility. 1460 61

To isolate cDNAs for molecules involved in cell adhesion to the extracellular matrix, expression cloning with non-adherent colon cancer Colo201 cells was carried out. Four positive clones were isolated and, when sequenced, one was found to be galectin-1, a beta-galactoside-binding protein. When cultured on fibronectin-, laminin-, and collagen-coated and non-coated dishes, the adherent galectin-1 cDNA-transfected Colo201 cells increased and spread somewhat. Immunofluorescence staining revealed that galectin-1 was expressed inside and outside of Colo201 cells. The adhesion was dependent on the carbohydrate-recognition domain of galectin-1 since lactose inhibited the adhesion and exogenously-added galectin-1 caused the adhesion. PD58059, an inhibitor of mitogen-activated protein kinase, or LY294002, a phosphoinositide 3-OH kinase inhibitor, decreased the adhesion. Furthermore, the expression of galectin-1 in Colo201 cells induced apoptotic cell death, while exogenously-added galectin-1 did not cause apoptosis. These results indicate that galectin-1 plays a role in both cell-matrix interactions and the inhibition of Colo201 cell proliferation, and suggest that galectin-1 expressed in cells could be associated with apoptosis.
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PMID:Galectin-1 induces cell adhesion to the extracellular matrix and apoptosis of non-adherent human colon cancer Colo201 cells. 1476 76

The mechanisms by which growth factors cooperate with cell adhesion molecules to modulate epithelial cell motility remain poorly understood. Here, we investigated the role of the E-cadherin/catenin complex in insulin-like growth factor (IGF-I)-dependent cell migration and invasion. We used variants of the HCT-8 colon cancer family that differ in their expression of alphaE-catenin, an intracellular molecule that links the E-cadherin/catenin complex to the actin cytoskeleton. Migration was determined using a monolayer wound model and cell invasion by the penetration of the cells into type-I collagen gels. We showed that alpha-catenin-deficient cells were not able to migrate in cohort upon IGF-I stimulation. Transfection of these cells with alpha-catenin isoforms (alphaN- or alphaT-catenin) restored migratory response IGF-I. These results suggest that alpha-catenins are involved in the signal issued from the E-cadherin/catenin complex to regulate IGF-I-stimulated migration. In contrast, IGF-I promoted invasion of both alpha-catenin-deficient and alpha-catenin-expressing cells, indicating that alpha-catenin did not participate in the regulation of IGF-I-induced invasion. Inhibition of E-cadherin function by treatment with MB-2 monoclonal antibodies inhibited both IGF-I-dependent cell migration and invasion. Taken together, our results indicate that functional alpha-catenin is essential for migration but not for invasion, while E-cadherin is involved in both phenomena.
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PMID:Alpha-catenin is required for IGF-I-induced cellular migration but not invasion in human colonic cancer cells. 1496 Oct 74

We have previously described the occurrence, in breast and colon cancer extra-cellular matrix, of an oncofoetal form of collagen, OF/LB, able to induce an increase in cell proliferation and motility in the breast cancer cell line 8701-BC. It also caused an increased amount of type V collagen which appears to exert an anti-proliferative effect on the same cells. The aim of the present study was to investigate, at the proteomic level, the effect of OF/LB and type V collagens used as substrates for neoplastic cell growth. Due to the complexity of a whole proteomic profile, a subset of significant protein classes was used to assess variations in protein expression levels. For this study we adopted a multivariate statistical procedure that allows a global view of the variations induced by different growth conditions, when several variables have to be analyzed simultaneously. The results of this research indicate that in response to different growth substrates, chaperons and heat shock proteins contributed most to the dissimilarity in levels of expression of the selected protein spots. Moreover, we observed that different isoforms of the same protein showed independent levels of expression from one another in relation to the different collagen treatments.
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PMID:Effect of collagen substrates on proteomic modulation of breast cancer cells. 1499 5

Apoptosis of the target cells is an important index in the assessment of the efficacy of cancer chemotherapy. We previously established a new experimental technique in which cancer cells are distributed in thin collagen gel as one or two cell layers, and cultured with anti-cancer drugs. The cells are stained with fluorescent Hoechst 33258 (Ho) and photographed, then with hematoxylin and eosin (H&E) and again photographed. The results show that most cell death patterns can be determined by combining observations of Ho and H&E-stained cells without the necessity for judging the apoptosis by electron microscopy. 5-fluorouracil (5-FU) and cisplatin (CDDP) are important anti-cancer drugs in the treatment of a variety of cancers. 5-FU or CDDP alone have shown significant effects in the treatment of gastric and colon cancers, and in addition, it has been shown that the combination of 5-FU plus CDDP (FP) therapy produces synergism greater than 5-FU or CDDP alone in gastrointestinal cancer. In this study, we evaluated the efficacy and toxicity of FP therapy in the gastric cancer cell lines MKN45, MKN28, and KATOIII and the colon cancer cell lines HCT116 and COLO320, and examined the relationship between the response to FP therapy and apoptosis. Additionally, we performed transfection of normal p53 gene into p53 mutant MKN28 cells and analyzed the impact of the p53 gene on a sensitivity test. Wild-type p53 in MKN45, HCT116, and COLO320 cells underwent significantly (p<0.01) more apoptosis than MKN28 and KATOIII cells possessing p53 mutant- and deficient-type, respectively, in FP therapy. Transfection of p53 to MKN28 cells resulted in a significantly (p<0.01) higher apoptotic index. From these results, we conclude that the p53 pathway allows induction of apoptosis in gastrointestinal cancers in FP therapy treatment, and that identification of the p53 type of a patient's cancer can be used to predict the success of FP therapy.
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PMID:Expression of p53 protein as a predictor of the response to 5-fluorouracil and cisplatin chemotherapy in human gastrointestinal cancer cell lines evaluated with apoptosis by use of thin layer collagen gel. 1501 Aug 16

Myofibroblasts are present at the invasion front in colon cancer. In an attempt to understand their putative proinvasive activity, we have developed an in vitro model. Myofibroblasts isolated from colon cancer tissue or obtained through transdifferentiation of colon fibroblasts by transforming growth factor (TGF)-beta stimulate invasion of colon cancer cells into collagen type I and Matrigel. We identified two convergent proinvasive agents secreted by myofibroblasts: namely scatter factor/hepatocyte growth factor (SF/HGF) and the TGF-beta-upregulated extracellular matrix glycoprotein tenascin-C (TNC), each of which is necessary though not sufficient for invasion. Myofibroblast-stimulated invasion into collagen type I is characterized by a change from a round, nonmigratory morphotype with high RhoA and low Rac activity to an elongated, migratory morphotype with low RhoA and high Rac activity. RhoA inactivation is determined by the epidermal growth factor (EGF)-like repeats of TNC through EGF-receptor signaling that confers a permissive and priming signal for the proinvasive activity of SF/HGF that activates Rac via c-Met. We confirmed the validity of this mechanism by using pharmacological modulators and dominant negative or constitutive active mutants that interfere with RhoA-Rho kinase and Rac signaling. Our in vitro results point to a new putative proinvasive signal for colon cancer cells provided by myofibroblasts in the tumor stroma.
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PMID:Tenascin-C and SF/HGF produced by myofibroblasts in vitro provide convergent pro-invasive signals to human colon cancer cells through RhoA and Rac. 1505 78

Malignant cells shed from tumors during surgical resection or spontaneous metastasis experience physical forces such as shear stress and turbulence within the peritoneal cavity during irrigation, laparoscopic air insufflation, or surgical manipulation, and within the venous or lymphatic system. Since physical forces can activate intracellular signals that modulate the biology of various cell types in vitro, we hypothesized that shear stress and turbulence might increase colon cancer cell adhesion to extracellular matrix, potentiating metastatic implantation. Primary human malignant colon cancer cells isolated from resected tumors and SW620 were subjected to shear stress and turbulence by stirring cells in suspension at 600 rpm for 10 min. Shear stress for 10 min increased subsequent SW620 colon cancer cell adhesion by 40.0 +/- 3.0% (n = 3; P < 0.001) and primary cancer cells by 41.0 +/- 3.0% to collagen I when compared to control cells. In vitro kinase assay (1.5 +/- 0.13 fold) and Western analysis (1.34 +/- 0.04 fold) demonstrated a significant increase in Src kinase activity in cells exposed shear stress. Src kinase inhibitors PP1 (0.1 microM), PP2 (20 microM), and actin-cytoskeleton stabilizer phalloidin (10 microM) prevented the shear stress stimulated cell adhesion to collagen I. Furthermore, PP2 inhibited basal (50.0 +/- 2.8%) and prevented shear stress induced src activation but phalloidin pretreatment did not. These results raise the possibility that shear stress and turbulence may stimulate the adhesion of malignant cells shed from colon cancers by a mechanism that requires both actin-cytoskeletal reorganization an independent physical force activation of Src kinase. Blocking this pathway might reduce tumor metastasis during surgical resection.
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PMID:Colon cancer cell adhesion in response to Src kinase activation and actin-cytoskeleton by non-laminar shear stress. 1510 61


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