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

The effect of transformation on the expression and the functions of beta 1 integrins was studied using an in vitro cell transformation model. S115 mammary epithelial tumor cells undergo transformation into tumorigenic fibroblastoid cells in the presence of steroids. Transformation was found to reduce the attachment and the spreading of S115 cells on laminin-1 but not fibronectin. Adhesion of S115 cells to laminin-1 was inhibited in the presence of an antibody against the beta 1 integrin subunit. Both nontreated and transformed S115 cells expressed at least two putative laminin-1-binding beta 1 integrins at the same level. In transformed cells, however, the mature integrin subunits appeared to be structurally altered, showing a slower electrophoretic mobility. Treatment with N-glycosidase-F and tunicamycin abolished this mobility difference, suggesting that the presence of complex-type N-linked oligosaccharides was responsible. Detailed enzymatic analysis of the oligosaccharides present on the beta 1 subunits revealed that the difference in glycosylation is, at least partially, due to poly-N-lactosaminoglycan chains on beta 1 integrin from transformed cells. Removal of this difference in glycosylation by either cleavage of the polylactosaminoglycan chains with endo-beta-galactosidase or inhibiton of complex-type glycan formation with swainsonine repeatedly enhanced the spreading of transformed cells on laminin-1. Thus, the increased size of complex-type oligosaccharides on beta 1 integrin may affect cell-laminin-1 interactions. Similar changes may contribute to the altered adhesion of cancer cells during the invasion and metastasis.
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PMID:Increased glycosylation of beta 1 integrins affects the interaction of transformed S115 mammary epithelial cells with laminin-1. 754 7

Adhesion molecules, including integrins, are important for interactions of cancer cells with vessel walls, a step leading to cancer metastasis. Disintegrins block the action of integrins by binding to them. We tested the hypothesis that the disintegrin eristostatin would block metastasis by interfering with cancer cell adhesion to vessel walls, thus preventing extravasation. Experimental metastasis assays, in which B16F1 melanoma cells (controls vs eristostatin-treated, 25 micrograms/ml) were injected via mesenteric veins of anesthetized C57BL/6 mice, showed that eristostatin reduced (P < 0.05) the mean number of liver metastases from 14.4 to 0.6 at 11 days postinjection (p.i.). We examined three different steps in metastasis at which eristostatin could have exerted its effect, namely, cell arrest, extravasation, and migration. Control and eristostatin-treated B16F1 cells were fluorescently labeled and examined by videomicroscopy in liver microcirculation in vivo at various times up to 14 days p.i. Measurements of vessel size in which cell arrest occurred and length/width ratio of arrested cells showed only small differences between control and eristostatin-treated cells. Eristostatin treatment did not prevent extravasation, and the timing and process of extravasation were similar for both treated and control cells; by 3-4 days p.i. more than 90% of the cells had extravasated or were in the process. Eristostatin also did not affect the ability of extravasated cells to migrate through the extracellular matrix to the subcapsular region where tumors later form. Therefore, we conclude that eristostatin exerted its primary effect by regulating the number of individual cancer cells that grow after extravasation.
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PMID:Effects of the disintegrin eristostatin on individual steps of hematogenous metastasis. 764 9

Adhesion to vascular endothelium is a primary step in the colonization of select target organs by blood-borne cancer cells. Previous studies in our laboratory have shown that adhesion is followed by the establishment of fully functional gap junctional channels between the arrested tumor cell and the endothelium and that gap junctional communication might play an important role in extravasation. Here we report on a critical interdependence between endothelial cell adhesion and communication of lung-metastatic cancer cells. Gap junctions are assembled at focal adhesion contacts between tumor cells and endothelial cells where they mediate metabolic coupling between the junction-forming cell pair. The level of coupling depends on sufficient amounts of connexin43 (cx43) protein expression by both cell partners and, in a rate-limiting fashion, on the expression level of the receptor/ligand pair that mediates adhesion between tumor cells and the endothelium. This conclusion is based on our findings that (a) tumor cells with equal cx43 message, yet different adhesion potential for endothelial cells, differ significantly in their level of communication with the endothelium (e.g., R230AC-MET vs. R3230AC-LR), and (b) gap junctional communication between B16-F10 melanoma cells and lung-matrix-modulated endothelium can be effectively blocked by antiadhesive, anti-Lu-ECAM-1 monoclonal antibody 6D3 and by soluble Lu-ECAM-1. Significantly increased adhesion and communication levels in highly lung-metastatic carcinoma cells imply a role of gap junctional coupling in cancer metastasis, presumably by facilitating extravasation.
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PMID:Adhesion-mediated gap junctional communication between lung-metastatatic cancer cells and endothelium. 765 9

Adhesion molecules are membrane proteins responsible for the complex functions of cell adhesion and cellular recognition and are thus of importance in inflammatory as well as neoplastic diseases. Adhesion molecules seem to play a significant role at each level of the metastatic cascade, including the destruction of normal cell-cell as well as cell-substrate cohesion, the penetration of tumor cells into the vascular system and the further spread into distant organs. In this summary an overview of subtypes, structure and function of the major groups of adhesion molecules is given and their possible role in the development, propagation and metastatic spread of malignancies discussed. Cell adhesion and its defects may be of importance in the behaviour of tumor cells and their spread. A better understanding of their function and possible manipulation of their expression, e.g., by cytokines could provide new therapeutic approaches in clinical oncology.
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PMID:[The significance of adhesion molecules in oncology]. 767 83

Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on pancreas carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic carcinoma cells to inflamed sites.
Int J Cancer 1993 Jul 30
PMID:Importance of E-selectin (ELAM-1) and sialyl Lewis(a) in the adhesion of pancreatic carcinoma cells to activated endothelium. 768 90

Adhesion molecules such as CD2 and its ligand CD58 (LFA-3), as well as CD11a/18 (LFA-1) and CD54 (ICAM-1) regulate not only cell to cell attachment but also participate in lymphocyte activation, recirculation, and effector function including cytolytic activity towards tumor cells. We have investigated the role of CD2/CD58 and CD11a/18/CD54 interactions in cellular immune responses directed towards freshly recovered human T cell leukemias. Downregulation of CD54 and CD58 were observed to correlate with enhanced numbers of blasts in circulation and lack of susceptibility to killing by autologous cytotoxic lymphocytes. Furthermore, culturing tumor cells with recombinant TNF-alpha conditioned medium resulted in reinduction of CD54 and CD58 expression and susceptibility to lymphocyte mediated resulted in reinduction of CD54 and CD58 expression and susceptibility to lymphocyte mediated lysis in vitro. Our findings support the view that adhesion molecules play a pivotal role for tumor cell biology in vivo and stress the point that successful immunotherapy of malignant disease may be facilitated by influencing not only the immune response itself but also adhesion molecules on the malignant tumor targets.
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PMID:Biological response modifiers render tumor cells susceptible to autologous effector mechanisms by influencing adhesion receptors. 769 Jun 30

Transfection of murine metastatic B78H1 cells (derived from B16 melanoma) with a syngeneic H-2Kb gene was used to study the effect of Major Histocompatibility Complex (MHC) gene products on tumour cell adhesion to endothelial cells and matrix proteins and the involvement in the metastatic process. H-2Kb-expressing transfectants showed a reduced adhesion to endothelial surfaces of different origin (four murine endotheliomas and human umbilical vein endothelial cells) when compared to parental B78H1 cells and to controls transfected with pSV2neo alone. On the average a 50-70% reduction in adhesion to endothelial cells was observed among H-2Kb transfectants. H-2Kb transfectants had a reduced expression of the alpha 4 integrin subunit, moreover the adhesion of Neo-transfected clones to endothelial cells was reduced to the levels of H-2Kb transfectants by antibodies directed against the beta 1 subunit and the endothelial VCAM-1 molecule, thus suggesting an impairment of the VLA-4/VCAM-1 interaction in H-2Kb transfectants. Adhesion to extracellular matrix components was also strongly decreased: in general the adhesion of H-2Kb cells showed a 50-75% inhibition with respect to Neo or parental controls. The highest difference was observed in adhesion to vitronectin and laminin, the lowest in adhesion to fibronectin. Reduction in adhesive properties of H-2Kb-expressing transfectants could be involved in the reduced metastatic ability, evaluated by means of intravenous injection of cells: H-2Kb transfectants yielded less than ten lung colonies, while all controls produced more than 100. Our data indicate that expression of a single class I MHC gene can significantly alter the metastatic phenotype of MHC-negative tumour cells and this could be related to a general alteration of tumour cell adhesive interactions.
Br J Cancer 1993 Nov
PMID:Decreased adhesion to endothelial cells and matrix proteins of H-2Kb gene transfected tumour cells. 769 18

The integrins are a large family of cell adhesion receptors, involved in cell-cell and cell-matrix interactions. At present, 20 different integrin heterodimers are known. They not only anchor cells to their proper locations, but also activately mediate the passage of information into the cell. They are involved in such diverse processes as immune response, lymphocyte homing, platelet aggregation, metastatic spread of certain malignancies, healing process of tissue injuries and, embryologic development. The role of integrins in reproduction had been only recently suggested. Several reasons make these molecules very attractive, due to their constant involvement from egg to birth. A normal expression of integrins can disrupt every reproductive stage. Most likely diagnostic tools and therapeutic propositions will emerge from the knowledge of these receptors. Integrins are a family of membrane glycoproteines that mediate cell-substratum or cell-cell adhesion. In respect of one fundamental principle of cellular biology consisting of 'what a cell touches has a major role in determining what a cell does', adhesion has a main part in many cell functions. Adhesion not only anchors cells to their proper locations, but also activately mediates the passage of information into the cell. Cellular adhesion is implicated in the immune response, lymphocyte homing, platelet aggregation, metastatic spread of certain malignancies, embryologic development and wound healing. The role of integrins in reproduction appears interesting. The aim of this review is to introduce these molecules, to outline their roles in cellular function and to consider their involvement in reproduction before foreseeing their potential implications for therapy.
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PMID:Integrins and reproduction. 778 65

Twelve different human primary and metastatic Ewing's sarcoma (ES) and primitive peripheral neuroectodermal tumour (pPNET) cell lines were examined by fluorocytometric analysis for the expression of alpha 1, alpha 2, alpha 3 and alpha 6 very late antigen (VLA) beta 1-integrins. VLA-alpha 1, was abundantly expressed on all typical ES cell lines and pPNET cell lines, while absent from atypical (large cell) ES cells. VLA-alpha 2 was displayed on some ES and pPNET cell lines. In two different pPNET cell lines, derived from the same patient, VLA-alpha 2 expression was considerably higher on primary cells compared with metastatic cells. VLA-alpha 3 was exclusively expressed on pPNET cell lines. Expression of VLA-alpha 6 was higher on metastatic than on primary ES and pPNET cells. Adhesion assays on purified extracellular matrix (ECM) proteins, using monospecific adhesion-blocking antibodies, disclosed VLA-1 (alpha 1 beta 1) on typical ES cells and pPNET cells, and VLA-2 (alpha 2 beta 1) on atypical ES cells, as dual collagen type IV (COIV)/laminin (LM) binding sites, and VLA-6 (alpha 6 beta 1) as a specific LM binding site. Treatment of typical ES cells and pPNET cells for up to 48 h with recombinant human interferon-gamma (rhIFN gamma) and tumour necrosis factor-alpha (rhTNF alpha) upregulated alpha 1 and beta 1 expression, concomitant with an increase in cell adhesion to COIV and LM. Alternatively, these cytokines downregulated the expression of alpha 2, alpha 6 and beta 1 on atypical ES cells, concomitant with a decrease in the adhesion to COIV and LM. In conclusion, these findings suggest that the difference in repertory of CO and LM integrin receptors on ES cells and pPNET cells reflects tumour status and degree of differentiation. Furthermore, our data indicate that IFN gamma- and TNF alpha-mediated alteration in the level of expression of distinct VLAs on ES and pPNET cells is correlated with changes in the adhesive behaviour of these tumour cells.
Eur J Cancer 1994
PMID:Expression of functional very late antigen-alpha 1, -alpha 2, -alpha 3 and -alpha 6 integrins on Ewing's sarcoma and primitive peripheral neuroectodermal tumour cells and modulation by interferon-gamma and tumour necrosis factor-alpha. 785 12

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.
Cancer 1995 Mar 15
PMID:Fucosyltransferase of the peritoneum contributed to the adhesion of cancer cells to the mesothelium. 788 88


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