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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prolonged glucocorticoid treatment causes osteoporosis in vivo and inhibits bone formation in vitro. We have previously shown that glucocorticoids inhibit calcification and alter osteoblast organization in a mineralizing bone organ culture system. In this study, the effect of glucocorticoids on osteoblast adhesion to bone matrix proteins and integrin expression was examined in primary rat osteoblasts and a transformed rat osteosarcoma-derived cell line ROS 17/2.8. After 24 h of treatment with corticosterone, these cells displayed a concentration-dependent decrease in adhesion to type I collagen and fibronectin. Adhesion was significantly decreased as early as 4 h after glucocorticoid administration. With 100 nM corticosterone treatment for 24 h, inhibition of the adhesion of ROS 17/2.8 cells and primary osteoblasts to fibronectin was 75 +/- 10% and 50 +/- 8%, and inhibition of adhesion to collagen was 31 +/- 10% and 65 +/- 5%, respectively. This effect was specific for osteoblasts, because glucocorticoids did not change the adhesion of fibroblasts. However, glucocorticoids did inhibit the adhesion of all cell types to rat osteonectin. To determine whether the change in osteoblast attachment to collagen and fibronectin was due to an alteration in integrin levels, the plasma membranes of these cells were labeled with [125I]lactoperoxidase, solubilized, and immunoprecipitated with an antibody to beta 1. A 24-h treatment with 100 nM corticosterone caused 80 +/- 2% and 64 +/- 9% decreases in beta 1 levels in primary osteoblasts and ROS 17/2.8 cells, respectively. These results were confirmed with immunofluorescence microscopy, which showed a glucocorticoid-induced decrease in beta 1 staining. Treatment of primary rat osteoblasts and ROS 17/2.8 cells for 72 h with corticosterone also decreased beta 1-integrin messenger RNA levels in a dose-dependent manner. We have demonstrated that the inhibition of integrin expression by glucocorticoids is involved in the decrease in osteoblast adhesion to bone extracellular matrix proteins. These data suggest that integrin modulation may influence osteoblast function and bone formation and, thus, contribute to glucocorticoid-induced osteoporosis.
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PMID:Glucocorticoids inhibit the attachment of osteoblasts to bone extracellular matrix proteins and decrease beta 1-integrin levels. 753 Jun 48

Interactions between cells and extracellular matrix are in large part mediated by integrins in divalent cation-dependent processes. Integrins are important for cell differentiation, proliferation, and migration during development and repair of diverse tissue types. The roles played by integrin adhesion receptors in the lung are just beginning to be investigated. It is plausible that integrins play a central role in mediating lung basement membrane influences on alveolar epithelial type II cell localization and differentiation. The current studies were carried out to determine the patterns of alveolar epithelial cell adherence and spreading on different substrata and their divalent cation and RGD requirements. We utilized a rat type II cell-derived cell line, LM5, and a human alveolar cell carcinoma cell line A549. Both cell types showed similar responses to divalent cations. Adhesion and spreading on different extracellular matrix components had different divalent cation requirements. Mn2+ enhanced adhesion and spreading on fibronectin (FN), type IV collagen, and laminin, but not on type I collagen or plastic. Mn(2+)-enhanced cell adhesion to FN was RGD-dependent and partially inhibited by an anti-alpha 5 integrin antibody. Small increases in Ca2+ concentration (0.1-0.5 mM), but not Mg2+, suppressed Mn(2+)-mediated adhesion and spreading. Thus, variations in the relative divalent cation concentrations in the vicinity of the integrin-ligand complex may modulate the receptor-acceptor interactions. These results support the view that alterations in extracellular divalent cations are important regulators of alveolar epithelial cell interactions with lung basement membrane.
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PMID:Divalent cation-dependent regulation of rat alveolar epithelial cell adhesion and spreading. 802 Jun 8

Since vascular complications in diabetes mellitus are attributed in part to blood platelets, our study tested the hypothesis that adhesion of platelets to collagen is enhanced in diabetic subjects. Platelet adhesion kinetics to type I collagen in the presence of plasma were evaluated by a new continuous-flow, micro-adhesion assay combined with resistive-particle counting to detect the loss of single platelets between 0.3 and 2.3 sec. Adhesion was also studied in a magnesium-containing Krebs-Ringer buffer to help assess whether the platelets themselves might be abnormal. We did not observe any differences in adhesion kinetics to collagen between the insulin-dependent (type I), the non-insulin dependent (type II) diabetics and the control subjects for platelets suspended in plasma or in washed platelets (p > 0.05). These findings suggest that platelet adhesiveness to type I collagen is not enhanced in diabetic subjects and is unlikely to contribute to the development of vascular complications.
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PMID:Platelet adhesion to collagen under flow conditions in diabetes mellitus. 804 94

It is now clear that adhesive interactions play a critical role in the process of metastatic tumor dissemination. Adhesion molecules act as both positive and negative modulators of the metastatic process. Molecules such as E-cadherin that promote homotypic tumor cell adhesion function to maintain intercellular contacts that confine cells to the primary tumor site and are negatively correlated with metastatic potential. Because tumor cells are rapidly eliminated from the circulation, those cells that can quickly arrest in the vasculature at a secondary site and pass through the vessel wall into the surrounding tissue will have a selective advantage toward establishing new metastatic colonies. The first step in this process is specific adhesion to venular endothelial cells in selected organs, a process mediated by tumor cell surface molecules such as Sialyl LewisX or the VLA-4 (alpha 4 beta 1) integrin that mediate binding to endothelial adhesion molecules such as the E-selectin or the vascular cell adhesion molecule, VCAM-1. Site-specific endothelial determinants such as the lung endothelial cell adhesion molecule, LuECAM, may additionally specify particular sites for preferential adhesion and subsequent site-specific metastasis of particular tumor types. After adherence to endothelial cells and subsequent endothelial retraction, metastatic tumor cells must adhere to elements of the subendothelial basement membrane such as laminin and types IV and V collagen, interactions frequently mediated by members of the beta 1 and beta 4 integrin families. Finally, metastatic tumor cell adhesion to connective tissue elements such as fibronectin, type I collagen and hyaluronan, mediated by molecules such as the beta 1 integrins and by the CD44 cell surface adhesion molecule, are required for movement of tumor cells into the subendothelial stroma and subsequent growth at these new sites. Thus, metastatic potential can be influenced both positively and negatively by a variety of cell surface adhesive molecules that act both independently and in concert to direct tumor cells to particular tissues, allowing them to arrest in those tissues, migrate across the vessel wall and grow at the secondary site. In the current review, I discuss the nature of the adhesion molecules that have been implicated in the metastatic process, emphasizing those molecules that have been shown to correlate with metastasis in clinical human tumors or that have been shown to influence metastatic potential in in vivo experimental assays.
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PMID:Adhesion molecules in tumor metastasis. 840 Jan 43

Prostatic carcinoma cells have a propensity to metastasize to bone, and we propose that this phenomenon may be promoted by the adhesion of metastatic cells to bone matrix. Bone matrix is produced by osteoblasts, and we have developed an in vitro model of bone matrix by isolating the substratum deposited by human osteoblast-like U2OS cells. The collagenous nature of this matrix was demonstrated by the incorporation of [3H]proline and its subsequent release by purified collagenase. Both U2OS matrix and purified type I collagen stimulated the adhesion of human PC-3 prostatic carcinoma cells. Human laminin supported adhesion to a much lesser extent, and PC-3 cells did not adhere to fibronectin. Adhesion of PC-3 cells to U2OS matrix closely resembled adhesion to purified type I collagen with respect to (a) inhibition by a collagen-derived peptide and by antibodies raised against alpha 2 or beta 1 integrin collagen receptor subunits; (b) lack of inhibition by RGD (Arg-Gly-Asp) peptides; (c) stimulation by Mn2+ and Mg2+ ions but not by Ca2+ ion; and (d) stimulation by the phorbol ester PMA (phorbol 12-myristate 13-acetate). This adhesion was also stimulated (2.3-fold) by transforming growth factor beta (TGF-beta), which is a major bone-derived growth factor. We conclude that human osteoblast-like matrix is an adhesive substrate for PC-3 prostate carcinoma cells. This adhesion appears to be mediated by the interaction of alpha 2 beta 1 integrin on PC-3 cells with matrix-derived collagen. The stimulation of this adhesion by TGF-beta suggests that the co-expression of TGF-beta and type I collagen in bone may synergistically facilitate the adhesion of metastatic cells to bone matrix proteins and thereby increase their localization in the skeleton.
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PMID:Bone cell matrix promotes the adhesion of human prostatic carcinoma cells via the alpha 2 beta 1 integrin. 852 12

This study describes the adhesion of human osteoblasts, cultured in vitro, to proteins of the extracellular matrix, the biosynthesis of integrins, their topography and organization in focal contacts. The adhesion of osteoblasts to laminin, type I collagen, vitronectin and fibronectin was 77-100%, in 2 h and at 55 nM substrata concentration, and it was accompanied by spreading of the cells. Adhesion to fibronectin (FN), laminin (LN) and type I collagen (COL) was inhibited by antibodies to the beta 1 integrin and antibodies to the alpha 5 chain affected adhesion only to fibronectin. Using a panel of polyclonal antibodies against alpha 2, alpha 3, alpha 5, alpha v, beta 1 and beta 3 integrins we detected synthesis of alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3, and an alpha v beta 1-like dimer by immunoprecipitation of metabolically labelled cell lysates. Studies of immunolocalization demonstrated the presence of the same integrins identified in lysates, plus alpha 4, alpha 1 and beta 5 subunits. In cells adhering in the presence of serum we showed organization of beta 3 and alpha v integrins in focal contacts. In cells adhering to fibronectin alpha 5 and beta 1 integrins were localized in focal contacts. In cells spread on laminin or type I collagen none of the integrins investigated was localized in focal contacts.
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PMID:Integrin synthesis and utilization in cultured human osteoblasts. 893 14

Migration of vascular smooth muscle cells (VSMC) is a key event in the formation of neointima during atherosclerosis. Fura-2 loaded VSMCs were used to investigate calcium homeostasis during cell migration. Multiple spontaneous transient increases in cytosolic free calcium [Ca(2+)](i)were observed in single human VSMCs migrating on type I collagen. Such [Ca(2+)](i)transients were dependent on the presence of serum or PDGF-BB. Removal of serum, or loading cells with BAPTA, abolished the transients and decreased cell migration speed. The transients were not affected by disruption of cell polarization by dihydrocytochalasin B. Adhesion was used to investigate the specific role of cell-substrate interactions in the generation of transients. Transients are seen in VSMCs adhering either on collagen or on poly-L-lysine, suggesting that generation of transients is not strictly dependent on integrins. Buffering [Ca(2+)](i) with BAPTA led to accumulation of (beta)1 integrins at the cellular tail, and to increased release of integrin on the extracellular matrix. These results demonstrate a role for [Ca(2+)](i) transients in the rapid, serum-dependent migration of VSMCs. These [Ca(2+)](i)transients are present in migrating VSMCs only when two simultaneous events occur: (1) substrate independent spreading and (2) stimulation of cells by serum components such as PDGF-BB.
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PMID:Migration of human vascular smooth muscle cells involves serum-dependent repeated cytosolic calcium transients. 1065 58

Human blood monocytes are attracted into connective tissues during early steps of inflammation and wound healing, and locally interact with resident cells and extracellular matrix proteins. We studied the effects of type I collagen on monocyte adhesion and superoxide anion production, using human monocytes elutriated from peripheral blood and type I collagen obtained from rat tail tendon. Both acid-soluble and pepsin-digested type I collagens promoted the adhesion of monocytes, whereas only acid-soluble collagen with intact telopeptides induced the production of superoxide. Adhesion and activation of monocytes on acid-soluble type I collagen depended on the presence of divalent cations. mAbs directed against integrin subunits CD11c and CD18 specifically inhibited adhesion and activation of monocytes on type I collagen. Protein membrane extracts obtained from monocytes were submitted to affinity chromatography on collagen I-Sepharose 4B, and analyzed by Western blotting using specific anti-integrin subunit Abs. In the case of both acid-soluble and pepsin-digested collagens, two bands were revealed with mAbs against CD11c and CD18 integrin subunits. Our results demonstrate that monocytes interact with type I collagen through CD11c-CD18 (alpha x beta 2) integrins, which promote their adhesion and activation. For monocyte activation, specific domains of the type I collagen telopeptides are necessary. Interactions between monocytes and collagen are most likely involved in the cascade of events that characterize the initial phases of inflammation.
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PMID:Human blood monocytes interact with type I collagen through alpha x beta 2 integrin (CD11c-CD18, gp150-95). 1082 Feb 75

MUC1 mucin expression has been shown to be associated clinicopathologically with metastasis and poor clinical outcome in a variety of tumors. To further investigate this finding experimentally, human pancreatic cancer S2-013 cells overexpressing MUC1 were used for spontaneous metastatic potential in nude mice. It was found that the number of lung metastases of MUC1 transfectants was significantly higher than that of control cells. To analyze the molecular mechanisms that underlie the increased metastatic activity, in vitro adhesion assays were performed. MUC1 mucin expression enhancedin vitro invasiveness and motility of S2-013 cells, and decreased the binding of S2-013 cells to type I collagen, Type IV collagen and laminin. Similar effects were not observed for cells expressing tandem repeat-deleted MUC1 cDNA. Adhesion properties were abolished by benzyl-alpha-GalNAc treatment, indicating that glycosylation of the extracellular domain of MUC1 was essential for these biological adhesive functions. Our data support the hypothesis that MUC1 expression contributes to the metastatic ability of pancreatic cancer cells.
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PMID:Enhancement of metastatic properties of pancreatic cancer cells by MUC1 gene encoding an anti-adhesion molecule. 1105 65

Hepatic stellate cells are located in the perisinusoidal space (space of Disse), and extend their dendritic, thin membranous processes and fine fibrillar processes into this space. The stellate cells coexist with a three-dimensional extracellular matrix (ECM) in the perisinusoidal space. In turn the three-dimensional structure of the ECM regulates the proliferation, morphology, and functions of the stellate cell. In this review, the morphology of sites of adhesion between hepatic stellate cells and extracellular matrix is described. Hepatic stellate cells cultured in polystyrene dishes spread well, whereas the cells cultured on or in type I collagen gel become slender and elongate their long cellular processes which adhere directly to the collagen fibers. Cells in type I collagen gel form a large number of adhesive structures, each adhesive area forming a face but not a point. Adhesion molecules, integrins, for the ECM are localized on the cell surface. Elongation of the cellular processes occurs via integrin-binding to type I collagen fibers. The signal transduction mechanism, including protein and phosphatidylinositol phosphorylation, is critical to induce and sustain the cellular processes. Information on the three-dimensional structures of ECM is transmitted via three-dimensional adhesive structures containing the integrins.
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PMID:Adhesion between cells and extracellular matrix with special reference to hepatic stellate cell adhesion to three-dimensional collagen fibers. 1128 Jul 3


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