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)

Starting from the BeWo choriocarcinoma cell line, two stable variant cell lines (epi and lc) were isolated. Epi cells displayed an epithelioid colony morphology while lc were fibroblastoid. lc cells attached and spread on fibronectin-coated surfaces at significantly lower density of fibronectin than epi or the parent cell line. lc also migrated more efficiently to fibronectin in a trans-filter assay than either epi or parent cells. Integrin expression by the cell lines was investigated by flow cytometry and immunoprecipitation from surface-labelled cells with a panel of subunit-specific antibodies. Integrins alpha 2 beta 1, alpha 5 beta 1, alpha v beta 1 and alpha 6 beta 4 were detected in each case, and levels of expression were identical in the two variant lines. Anti-functional antibodies were used to probe the role of integrins in fibronectin- and vitronectin-mediated adhesion. Complete inhibition of adhesion to fibronectin was observed with anti-beta 1 antibody, and partial inhibition with anti-alpha 5, suggesting that integrin alpha 5 beta 1 is mainly responsible for the interaction. Adhesion to vitronectin was inhibitable using anti-alpha v and anti-beta 1 antibodies, suggesting that integrin alpha v beta 1 is active in these cells as a vitronectin receptor. There was a correlation between the altered morphology of the variant cells and alterations in the distribution of integrin alpha 6 beta 4 and laminin in monolayer cultures. The results support the idea that fibronectin may mediate the migratory behaviour of extravillous trophoblast in vivo. Switch to a more migratory phenotype may be mediated by the selective activation of integrins and altered interaction with basement membrane.
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PMID:Variant choriocarcinoma (BeWo) cells that differ in adhesion and migration on fibronectin display conserved patterns of integrin expression. 147 45

The involvement of integrins in mediating interaction of cells to well-characterized proteolytic fragments (P1, E3, and E8) of laminin was assessed by antibody blocking studies. Cell adhesion to fragment P1 was affected by mAbs against the integrin beta 1 and beta 3 subunits and furthermore could be prevented completely by a synthetic peptide containing the Arg-Gly-Asp sequence. Because the beta 3 antibody-sensitive cell lines expressed the vitronectin receptor (alpha v beta 3) at high levels, the involvement of this receptor in cell adhesion to P1 is strongly suggested. Integrin-mediated cell adhesion to E3 is of low affinity and was inhibited by antibodies against the integrin beta 1 subunit. In contrast, adhesion of some cell types to E3 was not or only partially sensitive to inhibition by anti-integrin subunit antibodies. Cell adhesion to E8 was blocked completed by integrin alpha 6 or beta 1 antibodies. The alpha 6-specific antibody did not inhibit cell adhesion to E3 or P1. Furthermore, the antibody only blocked adhesion to laminin of those cells that adhered exclusively to the E8 fragment. In addition, expression of alpha 6 beta 1 was closely correlated with the ability of cells to bind to the E8 fragment of laminin. These results indicate that the alpha 6 beta 1 integrin is a specific receptor for the E8 fragment of laminin. Many cell types expressed, instead of or in addition to alpha 6 beta 1 the recently described integrin alpha 6 beta 4. Although the ligand of alpha 6 beta 4 was not identified, it must be different from that of alpha 6 beta 1, because cells that express alpha 6 beta 4, but not alpha 6 beta 1, do not adhere to E8, and cell adhesion to E8 was specifically blocked by beta 1 specific antibodies. In conclusion, the data indicate that distinct integrin receptors belonging to the beta 1 or beta 3 subfamily are involved in adhesion of cells to the various laminin fragments. Adhesion to E3 may also be brought about by other receptor molecules, possibly proteoglycans, not belonging to the integrin family.
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PMID:Integrin recognition of different cell-binding fragments of laminin (P1, E3, E8) and evidence that alpha 6 beta 1 but not alpha 6 beta 4 functions as a major receptor for fragment E8. 169 24

Current tissue culture techniques enable human keratinocytes (HK) from a small section of skin to be grown into sheets of epithelium for treating extensive wounds. The additional use of dermal replacements coupled with cultured skin substitutes may improve handling properties and effect ultimate healing results. Adhesion of cultured HK grafts to wounds, and final success rates of HK grafting, are variable and frequently unsatisfactory. To evaluate adhesion molecule (integrin) expression by cultured grafts, as well as matrix molecule distribution, we performed immunohistologic analysis of integrin expression on HK cultured on plastic and a polyurethane membrane, as well as on two dermal substitutes. Multilayered HK sheet grafts were prepared by culturing cells in plastic tissue culture dishes, and HK were cultured to single-layer confluence on polyurethane membranes (Hydroderm; Wilshire Medical Inc., Dallas, Texas). Composite grafts were prepared by seeding proliferating HK on Dermagraft, composed of human neonatal fibroblasts cultured in polyglactin mesh (Advanced Tissue Sciences, La Jolla, Calif.) and on AlloDerm, an acellular human dermis (LifeCell Inc., The Woodlands, Texas). Immunohistologic staining was performed for the integrin subunits alpha 5, alpha 6, and alpha v. Staining for matrix molecules included fibronectin, laminin-1, and laminin-5. HK in cultured epithelial sheets showed integrin alpha 6 expression on basal cells, and only faint alpha 5 and alpha v staining. HK cultured to confluence on Hydroderm reacted with monoclonal antibodies specific for alpha 5, alpha 6, and alpha v. Through HK adhered well to Dermagraft, there was reduced adhesion of HK on AlloDerm that was not accelerated by addition of fibronectin. HK in composite grafts showed distinct reactivity according to the time in culture. HK on Dermagraft lost alpha 5 reactivity by day 17 and only weak alpha v reactivity was seen. Basal keratinocytes on AlloDerm, however, remained alpha 5 and alpha v positive. In both composite grafts, integrin alpha 6 expression was limited to basal keratinocytes.
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PMID:Integrin and matrix molecule expression in cultured skin replacements. 873 66

It is well established that integrins and extracellular matrix (ECM) play key roles in cell migration, but the underlying mechanisms are poorly defined. We describe a novel mechanism whereby the integrin alpha 6 beta 1, a laminin receptor, can affect cell motility and induce migration onto ECM substrates with which it is not engaged. By using DNA-mediated gene transfer, we expressed the human integrin subunit alpha 6A in murine embryonic stem (ES) cells. ES cells expressing alpha 6A (ES6A) at the surface dimerized with endogenous beta 1, extended numerous filopodia and lamellipodia, and were intensely migratory in haptotactic assays on laminin (LN)-1. Transfected alpha 6A was responsible for these effects, because cells transfected with control vector or alpha 6B, a cytoplasmic domain alpha 6 isoform, displayed compact morphology and no migration, like wild-type ES cells. The ES6A migratory phenotype persisted on fibronectin (Fn) and Ln-5. Adhesion inhibition assays indicated that alpha 6 beta 1 did not contribute detectably to adhesion to these substrates in ES cells. However, anti-alpha 6 antibodies completely blocked migration of ES6A cells on Fn or Ln-5. Control experiments with monensin and anti-ECM antibodies indicated that this inhibition could not be explained by deposition of an alpha 6 beta 1 ligand (e.g., Ln-1) by ES cells. Cross-linking with secondary antibody overcame the inhibitory effect of anti-alpha 6 antibodies, restoring migration or filopodia extension on Fn and Ln-5. Thus, to induce migration in ES cells, alpha 6A beta 1 did not have to engage with an ECM ligand but likely participated in molecular interactions sensitive to anti-alpha 6 beta 1 antibody and mimicked by cross-linking. Antibodies to the tetraspanin CD81 inhibited alpha 6A beta 1-induced migration but had no effect on ES cell adhesion. It is known that CD81 is physically associated with alpha 6 beta 1, therefore our results suggest a mechanism by which interactions between alpha 6A beta 1 and CD81 may up-regulate cell motility, affecting migration mediated by other integrins.
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PMID:Integrin alpha 6A beta 1 induces CD81-dependent cell motility without engaging the extracellular matrix migration substrate. 936 67

Laminin-10/11, the laminin isoforms containing the alpha 5 chain, are major components of basement membranes of many fetal and adult tissues. Laminin-10/11 purified from the conditioned medium of human lung carcinoma cells were potent in mediating adhesion of the carcinoma cells in an integrin alpha 3 beta 1-dependent manner. To further define the type(s) of integrins involved in cell adhesion to laminin-10/11, we examined the effects of a panel of function-blocking anti-integrin antibodies on the adhesion of different cell types to laminin-10/11. Although anti-integrin beta 1 antibody inhibited the adhesion of all cell types tested, anti-alpha 3 antibody inhibited the adhesion of carcinoma and glioma cells but not fibroblastic cells. Adhesion of fibroblastic cells was inhibited, however, by a combination of anti-alpha 3 and anti-alpha 6 antibodies, suggesting that both alpha 3 beta 1 and alpha 6 beta 1 integrins function as laminin-10/11 receptors in these cells. To explore this possibility, we examined the adhesion of K562 leukemic cells transfected with integrin alpha 3 or alpha 6 subunit to laminin-10/11 or other laminin isoforms. Laminin-10/11 were potent adhesive ligands for both the alpha 3 beta 11 and alpha 6 beta 1 transfectants, whereas laminin-5 was the preferred ligand for the alpha 3 beta 1 transfectants. Upon stimulation with the activating anti-integrin beta 1 antibody, both transfectants became more adherent to the substratum regardless of the type of laminins coated, although their preference for laminin isoforms remained unaltered. K562 cells transfected with alpha 6 and beta 4 subunits were also capable of adhering to laminin-10/11, indicating that integrin alpha 6 beta 4 is another receptor for laminin-10/11. Even with lung carcinoma cells, the alpha 6-containing integrins partly contributed to adhesion to laminin-10/11 at higher coating concentrations, although non-integrin receptor(s) might also be involved under such conditions. These results indicated that laminin-10/11 are potent and versatile adhesive ligands in basement membranes capable of binding to both alpha 3 beta 1 and alpha 6 beta 1 integrins with high avidity and also to alpha 6 beta 4 integrin.
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PMID:Integrin binding specificity of laminin-10/11: laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrins. 1067 76