Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study adhesion, which is probably the initial step in malignant invasion, we associated tissue culture fragments with living substrates in vitro. Malignant HeLa, hepatoma, and PY cells, as well as nonmalignant BHK cells, were transplanted into cultured chick blastoderms and organ fragments from chick embryos. Adhesion was evaluated by time-lapse cinematography, by flushing with Tyrode's solution, and by histological examination after fixation. It was shown that the adhesion of these tissue culture fragments depends on the nature of the substrate. Substrates of connective tissue, mesenchyme, and the basal side of epithelia proved to be adhesive. In contrast, the apical side of intact epithelia was nonadhesive. Perforated epithelia allowed adhesion at the site of the perforation. In the presence of dilysine, HeLa cells adhere to the apical side of epithelia and to the dorsal side of the upper layer of the blastoderm. We concluded that the apical side of intact epithelia constitutes an inappropriate substrate for adhesion of a large variety of cells, in vitro as well as in vivo. Alteration of this characteristic in the presence of dilysine indicates that long-range electrostatic repulsion might be responsible for the nonadhesive character of the epithelia.
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PMID:Adhesion of malignant and nonmalignant cells to cultured embryonic substrates. 17 Oct 65

Cell-substratum adhesion of rat hepatocytes was inhibited by antisera raised against purified plasma membranes of rat liver (anti-liver-antiserum) and Morris hepatoma 7777 (anti-hepatoma-antiserum). It is assumed that substances which block the adhesion-inhibiting activity of the antisera are involved in cell-substratum adhesion. Adhesion-involved molecules of rat liver monitored as 'blocking activity' were compared with those of Morris hepatoma 7777 and 9121. They were found to be integral membrane glycoproteins, which could be solubilized only by detergents. Fractionation of plasma membrane extracts by size exclusion HPLC revealed two blocking activity peaks representing molecules involved in the adhesion to plastic (P-AIM) and collagen (C-AIM). In rat liver both adhesion-involved molecules were found; yet P-AIM seemed to be the major type of adhesion-involved molecule. In the relatively well differentiated Morris hepatoma 9121 also both types were detected. In membrane extracts of the high malignant and poorly differentiated Morris hepatoma 7777, however, no P-AIM but only C-AIM were found. Estimation by size exclusion HPLC revealed molecular weights of 120 kD for C-AIM and approx. 105 kD for P-AIM. On SDS gel electrophoresis proteins in the region of 95 kD were found in C-AIM containing fractions, whereas proteins of 105 kD are likely candidates for P-AIM.
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PMID:Integral membrane antigens involved in cell-substratum adhesion of hepatocytes and hepatoma cells. 670 41

The process and mechanism of peritoneal metastasis of tumor cells were studied experimentally by means of scanning or transmission electron microscopy, employing rat ascites hepatoma AH100B. Adhesion of tumor cells by microvilli and/or pseudopodia to the mesothelium was observed within 1 approximately 3 days after inoculation when there was no morphological changes of the mesothelial cells. Some changes of the mesothelial cells, such as irregularity, atrophy, and exfoliation, followed tumor cell adhesion 5 or 6 days after inoculation. It was noted that tumor cells adhered to the mesothelium first where no morphological changes were induced, and it is suggested that tumor cells infiltrate into the submesothelial tissue through mesothelial defects.
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PMID:A scanning electron microscopic study on the peritoneal implantation of ascites hepatoma AH100B cells in rats. 738 Jan 38

Adhesion and spreading of tumor cells to the films of a galactose-, glucose-, or phosphatidylcholine-bearing lipid was studied. Human adenocarcinoma Hela cells, B16 mouse melanoma cells, and HuH-7 human hepatoma cells selectively adhered and spread on galactose-bearing lipid in serum-containing medium, but not in serum-free medium. The spreading of the tumor cells in serum-containing medium was inhibited in the presence of lactose, but not in the presence of maltose. Cell spreading also occured on the galactose-bearing glycolipid film pre-treated with serum. From quantitative analysis for the the adsorption of serum components by a quartz-crystal microbalance, the surfaces of the lipid films were found to be entirely covered with serum components. These results suggested that serum components pre-adsorbed on the galactose-bearing lipid influence the cell spreading.
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PMID:The influence of serum for spreading of tumor cells on synthetic glycolipid films. 892 25

Adhesion of cancer cells to vascular endothelium is an important step in haematogenous metastasis of cancer. A human hepatocellular carcinoma cell line, HepG2, strongly adheres to human umbilical vein endothelial cells (HUVECs) through the interaction of E-selectin and its carbohydrate ligand sialyl Lewis X. In this study, we investigated alteration in integrin expression on HepG2 cells, which follows the selectin-mediated initial adhesion of HepG2 cells to HUVECs. Expression of alpha2beta1 integrin was markedly increased when the HepG2 cells adhered to HUVECs. Among the tested cytokines that are known to be produced by endothelial cells, recombinant hepatocyte growth factor (rHGF) could replace the effect of HUVECs, and a similar increase in integrin expression was observed by the addition of 20 ng ml-1 rHGF to HepG2. The increment of alpha2beta1 integrin expression was significantly inhibited by anti-HGF neutralizing antibody treatment. HepG2 cells expressed alpha2, alpha6, beta1, and beta4 integrin subunits, but expression of integrins other than alpha2beta1 was not affected by the rHGF treatment. The rHGF treatment of HepG2 cells resulted in augmented adhesion to immobilized collagen. This augmentation in adhesion to collagen was completely blocked by the addition of anti-alpha2- or anti-beta1-integrin antibody. In double-chamber chemoinvasion experiments, transmigration of the HepG2 cells through extracellular matrix (ECM) gel was significantly accelerated by co-cultivation with HUVECs. A similar level of enhancement in transmigration activity of the cancer cells was observed by the addition of rHGF. Our interpretation of the results described above is that the cancer cells received stimulation from cytokines, such as HGF, presented by vascular endothelial cells, following the initial adhesion of cancer cells via selectins. This resulted in the secondary increment in the expression of cell adhesion molecules, such as the alpha2beta1 integrin, and led to the augmented adhesive activities of cancer cells towards extracellular matrices at vascular walls. We suggest that this sequence of events is involved in the facilitated migration of some cancer cells to extravascular tissues.
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PMID:Involvement of hepatocyte growth factor in increased integrin expression on HepG2 cells triggered by adhesion to endothelial cells. 900 May 97

Adhesion of tumor cells to host cell layers and subsequent transcellular migration are pivotal steps in cancer invasion and metastasis. The small GTPase Rho controls cell adhesion and motility through reorganization of the actin cytoskeleton and regulation of actomyosin contractility. Cultured rat MM1 hepatoma cells migrate through a mesothelial cell monolayer in vitro in a serum-dependent, Rho-mediated manners. Among several proteins isolated as putative target molecules of Rho, the ROCK (ROK) family of Rho-associated serine-threonine protein kinases are thought to participate in the induction of focal adhesions and stress fibers in cultured cells, and to mediate calcium sensitization of smooth muscle contraction by enhancing phosphorylation of the regulatory light chain of myosin. Transfection of MM1 cells with cDNA encoding a dominant active mutant of ROCK conferred invasive activity independently of serum and Rho. In contrast, expression of a dominant negative, kinase-defective ROCK mutant substantially attenuated the invasive phenotype. A specific ROCK inhibitor (Y-27632) blocked both Rho-mediated activation of actomyosin and invasive activity of these cells. Furthermore, continuous delivery of this inhibitor using osmotic pumps considerably reduced the dissemination of MM1 cells implanted into the peritoneal cavity of syngeneic rats. These results indicate that ROCK plays an essential part in tumor cell invasion, and demonstrate its potential as a therapeutic target for the prevention of cancer invasion and metastasis.
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PMID:An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. 993 Aug 72

Adhesion of tumor cells to host cell layers and subsequent migration are pivotal steps in cancer invasion and metastasis. The small GTP-binding protein RhoA controls cell adhesion and motility through organization of the actin cytoskeleton and regulation of actomyosin contractility. Cultured rat MM1 hepatoma cells migrate through a mesothelial cell monolayer in vitro in a serum-dependent, RhoA-mediated manner (K. Yoshioka et al., J. Biol. Chem., 273: 5146-5154, 1998). Furthermore, the ROCK family of RhoA-associated serine-threonine protein kinases is involved in this migration, and an inhibitor for these kinases effectively inhibits the invasion of MM1 cells in vitro and in vivo (K. Itoh et al., Nat. Med., 5: 221-225, 1999). Although there have been no reports of genetic alterations directly affecting RhoA in human cancer, the expression level of RhoA in tumors has been several times higher than that of surrounding normal tissue; RhoA was especially highly expressed in the metastatic region. To determine whether RhoA is activated by its overexpression, we made stable transfectants of MM1 cells expressing various levels of wild-type human RhoA. These transfectants showed promoted invasive ability in vitro in the absence and presence of 1-oleoyl-lysophosphatidic acid, marked adherence to the plastic culture dish with scattered shape, elevated phosphorylation of Mr 20,000 myosin light chain, and translocation of RhoA protein from the cytosol to the membrane. All of these phenotypes were similar to those of active RhoA transfectants, correlated with the expression level of RhoA and reversed by the treatment of the cells with Clostridium botulinum exoenzyme C3 ADP-ribosyltransferase. In addition, overexpression of wild-type RhoA in MM1 cells also conferred invasive ability in vivo after the cells were transplanted into the syngeneic rats. Thus, high expression of RhoA in the cell facilitates the translocation of this protein to the membrane, where it is activated, resulting in the stimulation of the RhoA-ROCK-actomyosin system, leading to invasion.
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PMID:Overexpression of small GTP-binding protein RhoA promotes invasion of tumor cells. 1021 13

The aim of this randomized controlled trial was to assess the efficacy of interferon alfa-2b (IFN) for the treatment of advanced hepatocellular carcinoma (HCC). Fifty-eight patients with HCC who were not suitable for resection, transplantation, ethanol injection, or arterial embolization were stratified according to their Okuda stage and randomized to receive IFN (3 x 10(6), 3 times a week, for 1 year) (n = 30) or symptomatic treatment (n = 28). Both groups were identical in terms of age, sex, performance status, presence of constitutional syndrome, Child-Pugh class, Okuda stage, multinodularity, portal thrombosis, and extrahepatic spread. Adhesion to IFN treatment was adequate in 27 patients, with a mean duration of treatment of 8 +/- 3 months. However, IFN treatment was associated with side effects in 23 patients, leading to treatment discontinuation in 13 patients. Two of the 30 patients (6.6%) presented a partial response with greater than 50% size reduction and normalization of alpha-fetoprotein levels. The survival at 1 and 2 years according to intention to treat was not different between the 2 groups (58% and 38% vs. 36% and 12%, respectively, Breslow P =. 19, log rank P =.14) and the absence of difference was maintained when dividing patients according to their Okuda stage. The probability of presenting tumor progression (P =.17), or deterioration of Child-Pugh class (P =.37), performance status (P =. 07), or Okuda stage (P =.44) was not modified by IFN treatment. These results indicate that IFN is not properly tolerated in patients with cirrhosis and advanced HCC and that its administration prompts no benefit in terms of tumor progression rate and survival.
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PMID:Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. 1061 28

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.
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PMID:The prognostic molecular markers in hepatocellular carcinoma. 1204 56

A micropipette technique was used to investigate the effects of four synthetic peptides, YIGSR, CDPGYIGSR, RGDS and GRGDTP, on the adhesion of hepatocellular carcinoma (HCC) cells onto type IV collagen/laminin/fibronectin coated surfaces. Adhesion of HCC cells to laminin was found to be YIGSR- or CDPGYIGSR-dependent while that to fibronectin and type IV collagen was RGDS- or GRGDTP-dependent. The reduction in adhesion strengths of HCC cells was slight to moderate (up to 55%), and was dependent on the peptide concentration. The decrease in adhesion strengths was reversed by an increase in ligand coating concentration and was compromised by prolonged interaction of the cells with the surfaces. These results suggested that the inhibition was due to competitive retardation rather than to a blockade of adhesion strengthening. A simple asymptotic function was adopted to fit the correlation between the mean of cell adhesion strengths and peptide concentration within defined concentration ranges. Regression analysis showed that cell adhesion strengths appeared to approach a plateau with increasing concentration of the inhibitory peptides, which was not always uniform over the entire concentration range tested. Further reduction in adhesion strengths was observed at higher peptide concentrations. It is suggested that the constants obtained by fitting over a low peptide concentration range might be kinetically representative of the inhibition during early events of adhesion or attachment.
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PMID:Inhibition of adhesion of hepatocellular carcinoma cells to basement membrane components by receptor competition with RGD- or YIGSR-containing synthetic peptides. 1277 13


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