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

Transmembrane signals generated following mAb binding to CD19, CD20, CD39, CD40, CD43, Leu-13 Ag, and HLA-D region gene products induced rapid and strong homotypic adhesion in a panel of human B cell lines. Lower levels of adhesion were also observed after engagement of CD21, CD22, and CD23. Adhesion induced by mAb binding to these Ag was identical with respect to the kinetics of adhesion and the morphology of the resulting cellular aggregates, and was distinct from PMA-induced adhesion in both of these properties. Adhesion was not observed in response to mAb binding to MHC class I, CD24, CD38, CD44, CD45RA, or CD72. In contrast to B cell lines, homotypic adhesion was not induced in two pre-B cell lines, in spite of their high level expression of CD19 and HLA-D. Adhesion induced by suboptimal stimulation through these surface Ag or by PMA was mediated primarily through LFA-1 and ICAM-1. However, optimal stimulation through CD19, CD20, CD39, CD40, and HLA-D induced strong homotypic adhesion that was not blocked by anti-LFA-1 mAb. This alternate pathway of adhesion was also observed in LFA-1-deficient cell lines and in the presence of EDTA, suggesting that adhesion was not mediated by integrins. Adhesion in response to engagement of cell-surface Ag was unaffected by H7 or genestein, but was significantly inhibited by staurosporine, and was completely ablated by sphingosine and herbimycin. These studies indicate that engagement of multiple B cell-surface molecules initiates a signal transduction cascade that involves tyrosine kinases but not protein kinase C, and which leads to homotypic adhesion. Furthermore, adhesion was mediated by at least two distinct cell-surface adhesion receptors: LFA-1/ICAM-1 and a heretofore unknown adhesion receptor.
 ...
PMID:Transmembrane signals generated through MHC class II, CD19, CD20, CD39, and CD40 antigens induce LFA-1-dependent and independent adhesion in human B cells through a tyrosine kinase-dependent pathway. 172 39

The vascular cell adhesion molecule-1 (VCAM-1) plays an important role in diverse physiological and pathological processes. The homologous first and fourth immunoglobulin-like domains of the seven domain form of VCAM-1 present binding motifs for alpha 4 beta 1 integrin. Using a panel of VCAM-1 domain deletion mutants we show that alpha 4 beta 7 integrin interacts with both domains 1 and 4. In contrast to their identical domain usage, alpha 4 beta 1 and alpha 4 beta 7 integrins differ in the activation states required for binding to domains 1 and 4 of VCAM-1. We show that integrin alpha 4 beta 1 required significantly higher concentrations of Mn2+ than integrin alpha 4 beta 7 to support half-maximal adhesion to domain 4. Moreover, a clear difference in the capacity of integrins alpha 4 beta 1 and alpha 4 beta 7 to interact with domain 4 was detected in the presence of Ca2+ and Mg2+ cations. Adhesion to domain 1 of VCAM-1, however, was not affected by integrin heterodimer composition. Instead, the activity level of integrin alpha 4 beta 1 for domain 1 binding was regulated by CD24 expression. Binding to seven domain VCAM-1 was not altered significantly by beta 1 and beta 7 subunits or CD24. These data indicate that integrin heterodimer composition and CD24 expression differentially modulate integrin binding to domains 1 and 4 of VCAM-1. Mechanisms that alter integrin binding specificity or monovalent versus divalent interactions may affect the strength of adhesion as well as signal transmission in adherent cells and may therefore be critical to controlling the cellular response to integrin occupancy.
 ...
PMID:Differential regulation of alpha 4 integrin-dependent binding to domains 1 and 4 of vascular cell adhesion molecule-1. 753 4

Outcome in high-risk patients with refractory or relapsed germ cell tumours (GCT) remains poor. Novel strategies enhancing therapeutic efficacy whilst limiting therapeutic burden are warranted, yet immunotherapy approaches geared towards activating endogenous antitumor responses have not been successful thus far. Redirection of cytotoxic effector cells by bispecific antibodies represents a promising approach in this setting. We demonstrate that the Epithelial Cell Adhesion Molecule (EpCAM) is broadly expressed in GCT cell lines of different histologic origin including seminoma, choriocarcinoma (CHC), and embryonal carcinoma (EC). In these GCT lines of variable EpCAM surface expression, targeting T cells by the prototypic bispecific EpCAM/CD3-antibody (bAb) Catumaxomab together with natural killer (NK) cell engagement via the Fc domain promotes profound cytotoxicity across a broad range of antibody dilutions. In contrast, tumor cell lysis mediated by either immune cell subset alone is influenced by surface density of the target antigen. In the CHC line JAR, NK cell-dependent cytotoxicity dominates, which may be attributed to differential surface expression of immunomodulatory proteins such as MHC-I, CD24, and Fas receptors on CHC and EC. In view of redirecting T cell therapy mediated by bispecific antibodies, such differences in GCT immunophenotype potentially favoring immune escape are worth further investigation.
 ...
PMID:Targeting EpCAM by a Bispecific Trifunctional Antibody Exerts Profound Cytotoxic Efficacy in Germ Cell Tumor Cell Lines. 3243 48