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)

A panel of monoclonal antibodies (mAbs) to bovine fibronectin (FN) is described which modulates either heparin binding or cell adhesion to FN, or both. A combination of competitive exclusion and binding to proteolytic fragments identified epitopes in the Hep II, Hep III/I and CBF (cell binding fragment) regions of FN. mAb A17, which bound to the CBF region, strongly inhibited the cell adhesion of BHK-21 fibroblasts, primary corneal fibroblasts and endothelial cells, and NM4 mammary adenocarcinoma cells, to FN at mAb concentrations as low as 1 microgram/ml. This mAb was not so effective at inhibiting the adhesion of B16 mouse melanoma cells. Adhesion of B16 cells to FN was more sensitive to inhibition by mAbs binding to Hep II (A2, A9, A32, A35). Of these, A32 and A35 significantly increased the binding of 35S-heparin to FN, whereas A2 and A9 did not affect it. mAbs A2, A9 and A32 showed good binding to HBF, the 40 kDa proteolytic fragment of human FN which contains both Hep II and IIICS (type III connecting segment). These mAbs inhibited B16 cell adhesion to the HBF (heparin binding fragment) by 30-50%, the greatest inhibition being shown by mAb A32. Two synthetic peptides from the HBF, CS1 (peptide 1) from the IIICS region and peptide I from the Hep II region, also inhibited B16 cell adhesion to HBF by approximately 70 and 30%, respectively. These results suggest that maximal cell adhesion to the HBF involves both CS1 and Hep II. The inhibitory effects of the two peptides were linearly additive in combination, whereas the inhibitory mAbs A2, A9 and A32 showed synergistic additive effects with each of the peptides. This points to the existence of an additional important cell binding site in Hep II, other than peptide I. Recent independent evidence for an additional cell binding site in Hep II supports this view. Melanoma cellular receptor(s) for the Hep II region may be cell surface proteoglycans but do not appear to bind to areas of Hep II with high affinity for soluble heparin, as the latter was not an inhibitor of B16 cell adhesion to the HBF. The increased effectiveness of A32 in inhibiting cell adhesion, compared to A2 and A9, may be due to conformational effects which increase the binding of soluble heparin, but reduce affinity for the cellular receptor. These results are discussed in context with other reports in the literature.
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PMID:Anti-fibronectin antibodies that modify heparin binding and cell adhesion: evidence for a new cell binding site in the heparin binding region. 138 58

In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as by A9, a beta 4 specific antibody (30% inhibition). Most importantly, we demonstrate that alpha 6 beta 4 binds specifically to laminin-Sepharose columns in the presence of either Mg2+ or Mn2+ and it is eluted from these columns with EDTA but not with NaCl. The alpha 6 beta 4 integrin does not bind to collagen-Sepharose, but the alpha 2 beta 1 integrin does bind. Clone A cells do not express alpha 6 beta 1 as evidenced by the following observations: (a) no beta 1 integrin is detected in beta 1 immunoblots of GoH3 immunoprecipitates; and (b) no alpha 6 beta 1 integrin is seen in GoH3 immunoprecipitates of clone A extracts that had been immunodepleted of all beta 4 containing integrin using the A9 antibody. These data establish that laminin is a ligand for the alpha 6 beta 4 integrin and that this integrin can function as a laminin receptor independently of alpha 6 beta 1.
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PMID:The integrin alpha 6 beta 4 is a laminin receptor. 153 98

The invasion of malignant cells through the basement membrane is a critical step in local infiltration and metastasis. Adhesion and invasion of malignant cells may be modulated by their receptor mediated binding to the basement membrane glycoprotein laminin. We studied the specific adhesion of human colon adenocarcinoma derived HT 29 cells to laminin and its proteolytic fragments. The major cell adhesion domain of laminin was localised in the central part of the cross shaped molecule. Immunoblotting experiments on separated HT 29 cell membranes using specific antibodies or radiolabelled laminin fragments revealed two major laminin-binding cell surface components with Mr of 67,000 and 69,000 D similar to the putative laminin receptor described for other tissues. Using a nitrocellulose filter disk assay, the specific interaction between cell surface binding proteins and proteolytic fragments originating from the central core of the laminin molecule could be further corroborated. In contrast, interaction of HT 29 cell membranes with the pentapeptide YIGSR (tyr-ile-gly-ser-arg), a sequence domain of the B1-chain of the laminin molecule, thought to be responsible for cell adhesion, was significantly weaker.
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PMID:Identification of laminin binding proteins in cell membranes of a human colon adenocarcinoma cell line. 213 83

Several purified glycoproteins including laminin, fetuin, and human chorionic gonadotropin promote dose-dependent and saturable adhesion of Mycoplasma pneumoniae when adsorbed on plastic. Adhesion to the proteins is energy dependent as no attachment occurs in media without glucose. Adhesion to all of the proteins requires sialic acid, and only those proteins with alpha 2-3-linked sialic acid are active. The alpha-subunit of human chorionic gonadotropin also promotes attachment, suggesting that a simple biantennary asparagine-linked oligosaccharide is sufficient for binding. Soluble laminin, asparagine-linked sialyloligosaccharides from fetuin, and 3'-sialyllactose but not 6'-sialyllactose inhibit attachment of M. pneumoniae to laminin. M. pneumoniae also bind to sulfatide adsorbed on plastic. Dextran sulfate, which inhibits M. pneumoniae binding to sulfatide, does not inhibit attachment on laminin, and 3'-sialyllactose does not inhibit binding to sulfatide, suggesting that two distinct receptor specificities mediate binding to these two carbohydrate receptors. Both 3'-sialyllactose and dextran sulfate partially inhibit M. pneumoniae adhesion to a human colon adenocarcinoma cell line (WiDr) at concentrations that completely inhibit binding to laminin or sulfatide, respectively, and in combination they inhibit binding of M. pneumoniae to these cells by 90%. Thus, both receptor specificities contribute to M. pneumoniae adhesion to cultured human cells.
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PMID:Sialic acid-dependent adhesion of Mycoplasma pneumoniae to purified glycoproteins. 247 Jul 54

The in vitro adhesion rates of rat 13762NF mammary adenocarcinoma cell clones of different spontaneous metastatic potentials to cloned microvessel endothelial cell monolayers and their subendothelial extracellular matrix were investigated. In this system, high rates of adhesion of the cloned tumor cell lines to syngeneic target (lung) organ-derived subendothelial matrix correlated with spontaneous metastatic potential, whereas adhesion to the lung microvessel endothelial cell apical surfaces occurred at lower rates and was not highly significantly different among the tumor cell lines. Adhesion rates to bovine aortic large vessel, and human brain and human meningeal microvessel endothelial cell monolayers were, in general, lower than those found with syngeneic lung microvessel endothelial cells, and did not correlate with spontaneous metastatic potential. Growth of endothelial cells in fetal bovine serum or platelet-poor horse serum did not affect the results, suggesting that in this system metastasis-associated organ-adhesive specificity is determined at the level of the subendothelial matrix.
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PMID:Differential adhesion of metastatic rat mammary carcinoma cells to organ-derived microvessel endothelial cells and subendothelial matrix. 277 62

Human carcinomas of the pancreas are aggressive tumors which traverse basement membrane barriers during invasion and metastasis. In order to examine the relationship of pancreatic tumor cells to basement membranes, we analyzed and compared the capabilities of four biologically different human pancreatic adenocarcinoma lines to adhere to substrate coated with purified basement membrane constituents. Each of the four cell lines adhered readily to purified laminin in a dose-dependent manner, although differences were noted in the time required for optimum attachment. Significant variations in the abilities of the cell lines to attach to purified fibronectin were evident both in concentration dependence and in the time required for attachment and spreading. Adhesion to type IV collagen was negligible for two of the four tumor lines but addition of soluble laminin or fibronectin augmented attachment. The other two cell lines attached only moderately to type IV collagen and this attachment was not enhanced by soluble laminin or fibronectin. When laminin or fibronectin was coated directly over type IV collagen, attachment of all four cell lines was comparable to that for the glycoproteins alone. Although the tumor lines were all established from human neoplasms of similar histological origin and retained the ability to adhere to intact basement membranes prepared from human amnion, they exhibited various patterns of attachment to laminin, fibronectin, and type IV collagen.
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PMID:Diversity of adhesion to basement membrane components of human pancreatic adenocarcinomas. 293 15

A baculovirus system was used to express full-length recombinant mouse thrombospondin 2 (rTSP2) as a disulfide-bonded homotrimer with an NH2 terminus beginning with Asp20.rTSP2, like TSP1, was more sensitive to trypsin digestion if depleted of calcium ion. The trypsin digestion pattern of rTSP2 and TSP1 differed in that trypsin cut between the first and second type 1 modules of rTSP2. For bovine aortic endothelial cells adhering to TSP-coated polystyrene plates, reduction after coating caused both TSPs to be much more adhesive; these adhesions were blocked completely by RGDS peptide or antibody to alpha v beta 3 integrin.rTSP2 and TSP1 also mediated the adhesion of HT-29 human colon adenocarcinoma cells that carry alpha v beta 5 but not alpha v beta 3 integrin. Antibody to alpha v beta 5 did not inhibit adhesion of HT-29 cells to TSP1 or rTSP2. Rather, adhesion of HT-29 cells was decreased by treatment of TSPs with EDTA, abolished by reduction of the TSPs, and, in the case of rTSP2, blocked by heparin. Adhesion of MG63 cells to both TSPs was complex. Treatment with EDTA enhanced the adhesive activity of rTSP2 but decreased the adhesive activity of TSP1. These results show that TSP2 can be processed and secreted when overexpressed using baculovirus, TSP1 and rTSP2 differ in protease susceptibility in the type 1 module region, and TSP1 and rTSP2 mediate cell adhesion by complex and similar but not identical mechanisms.
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PMID:Properties of recombinant mouse thrombospondin 2 expressed in Spodoptera cells. 779 22

Adhesion molecules associating with peritoneal dissemination were investigated using human gastric (MKN45 and MKN74) and colon (KM12C and KM12SM) cancer cells and the mouse peritoneum. Adhesion of cancer cells to the peritoneum was determined by a recently reported novel ex vivo method. MKN45 cells established from poorly differentiated adenocarcinoma with less glycosylated sugar chains on their cell surface showed higher adhesion activities to the peritoneum ex vivo and produced large amount of metastases in the abdominal cavity of nude mice, whereas MKN74 cells from differentiated adenocarcinoma with more glycosylated sugar chains showed slightly low adhesion activity. KM12SM cells with highly metastatic potential to liver showed fairly low adhesion activity to the peritoneum compared with KM12C cells. The mouse peritoneum was found to contain alpha 1 --> 2, alpha 1 --> 3, and alpha 1 --> 4 fucosyltransferases, and adhesion of cancer cells was observed to the cellulose ester membrane, on which partially purified alpha-fucosyltransferases from mouse peritoneum were immobilized. The adhesion of cancer cells to fucosyltransferase-immobilized membrane was specifically inhibited by the addition of oligosaccharides and glycoproteins, which could serve as substrates for alpha-fucosyltransferases. These results indicate the contribution of alpha-fucosyltransferases to the adhesion of disseminated cancer cells to the peritoneum and support the possibility of antiadhesion therapy of peritoneal dissemination by treatment with substrates for alpha-fucosyltransferases.
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PMID:Fucosyltransferase of the peritoneum contributed to the adhesion of cancer cells to the mesothelium. 788 88

Ten small cell lung carcinoma and 12 non-small cell lung carcinoma cell lines of various histological types were studied for constitutive expression of the intercellular adhesion molecule-1 (ICAM-1). ICAM-1 was present in all squamous and large cell carcinoma cell lines whereas two out of five adenocarcinoma and all small cell lung cancer (SCLC) cell lines showed no basal ICAM-1 expression. ICAM-1 expression was upregulated by tumour necrosis factor-alpha (TNF-alpha) in a time- and dose-dependent manner in cell lines with basal ICAM-1 expression. Western blot analysis revealed a molecular size of 85 kDa for ICAM-1 in all but one cell line. The TNF-alpha-induced upregulation of ICAM-1 occurs on the transcriptional level. Adhesion of peripheral blood mononuclear cells to lung tumour cell lines could be inhibited by monoclonal antibodies (MAb) (CD11a;CD18) against the receptor of ICAM-1, the leukocyte function-associated antigen-1 (LFA-1), but not by a MAb (CD54) against ICAM-1 itself.
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PMID:Differential expression of the intercellular adhesion molecule-1 (ICAM-1) in lung cancer cell lines of various histological types. 811 Apr 95

The integrin mediated interactions between tumour cells and the surrounding extracellular matrix are thought to play crucial parts in the complex process of invasion and metastasis. It has been previously shown that the expression of integrins is differently diminished in a chain-specific manner in human colorectal cancer. To further characterise the integrins still expressed in colorectal carcinomas, immunoblots with monoclonal antibodies against the beta 1 integrin subunit have been performed. In isolated cell membranes of colorectal cancers a second smaller beta 1 chain (105 kD non-reduced) was found as well as the mature beta 1 chain (116 kD non-reduced) present in normal mucosa of the colon. This smaller beta 1 chain comigrates with the diminished glycosylated precursor form of the beta 1 chain. The role of N-glycosylation for the function and expression of integrins in vitro was therefore investigated, with deoxymannojirimycin (DMJ) and deoxynojirimycin (DNJ) as specific inhibitors of N-glycan processing. Pretreatment of human colon adenocarcinoma derived HT-29 cells with DMJ resulted in an expression of the 105 kD beta 1 precursor chain and of smaller forms of the alpha 1, alpha 3, alpha 6, and alpha v integrin subunits in a time and dose dependent manner. HT-29 cells treated with DMJ adhered poorly to laminin (8% of untreated controls), collagen type IV (40%), and fibronectin (35%). Pretreatment of the cells with DNJ did not alter the molecular weight of the integrin chains expressed and reduced HT-29 adhesion to laminin and fibronectin only to 68% and 49% respectively. Adhesion to collagen type IV was increased to 124% by DNJ. These results show that N-glycan processing is essential for the function and expression of integrins in human colorectal cancer cells. An altered glycosylation of these adhesion receptors may contribute to a more invasive or metastatic phenotype in colorectal cancer.
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PMID:Altered glycosylation of integrin adhesion molecules in colorectal cancer cells and decreased adhesion to the extracellular matrix. 831 18


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