Spatio-Temporally Restricted Expression of Cell Adhesion Molecules during Chicken Embryonic Development

Differential cell adhesive properties are known to regulate important developmental events like cell sorting and cell migration. Cadherins and protocadherins are known to mediate these cellular properties. Though a large number of such molecules have been predicted, their characterization in terms of interactive properties and cellular roles is far from being comprehensive. To narrow down the tissue context and collect correlative evidence for tissue specific roles of these molecules, we have carried out whole-mount in situ hybridization based RNA expression study for seven cadherins and four protocadherins. In developing chicken embryos (HH stages 18, 22, 26 and 28) cadherins and protocadherins are expressed in tissue restricted manner. This expression study elucidates precise expression domains of cell adhesion molecules in the context of developing embryos. These expression domains provide spatio-temporal context in which the function of these genes can be further explored.     

Role of Cell Adhesion Molecules and Immune-Cell Migration in the Initiation,Onset and Development of Atherosclerosis

Atherosclerosis is currently the leading factor of death in developed countries. It is now recognized as a chronic immune-inflammatory disease, whose initial stages involve the interaction of leukocytes with the endothelial monolayer. The initial stage of atherosclerosis requires the interplay of various cell adhesion molecules and immune cells to trigger leukocyte and lymphocyte migration from the circulating blood into the arterial intima. Studies have unveiled the role of inflammatory mediators in the initiation, onset and progression of the disease. During the last few years we have gained a greater understanding of the mechanism that modulates monocyte, macrophage and T cell infiltration, the role these cells play in the atherosclerotic lesion, in the formation of the fibrous plaque formation with the consequent narrowing of the arteries and the mechanisms that lead to plaque rupture and the formation of thrombi and emboli. This review talks about the leukocyte recruitment in early atherosclerosis, the formation of the plaque, and the mechanisms that lead to thrombosis in advanced atherosclerosis. Finally, we discuss the potential for novel therapies to treat this disease.Key Words: CAMs, leukocyte, lymphocyte, migration, atherosclerosis, extravasation     

Role of Cell Adhesion Molecules and Immune-Cell Migration in the Initiation,Onset and Development of Atherosclerosis

Atherosclerosis is currently the leading factor of death in developed countries. It is now recognized as a chronic immune-inflammatory disease, whose initial stages involve the interaction of leukocytes with the endothelial monolayer. The initial stage of atherosclerosis requires the interplay of various cell adhesion molecules and immune cells to trigger leukocyte and lymphocyte migration from the circulating blood into the arterial intima. Studies have unveiled the role of inflammatory mediators in the initiation, onset and progression of the disease. During the last few years we have gained a greater understanding of the mechanism that modulates monocyte, macrophage and T cell infiltration, the role these cells play in the atherosclerotic lesion, in the formation of the fibrous plaque formation with the consequent narrowing of the arteries, and the mechanisms that lead to plaque rupture and the formation of thrombi and emboli. This review talks about the leukocyte recruitment in early atherosclerosis, the formation of the plaque and the mechanisms that lead to thrombosis in advanced atherosclerosis. Finally, we discuss the potential for novel therapies to treat this disease.     

Modelling Cell Migration and Adhesion During Development

Cell?Ccell adhesion is essential for biological development: cells migrate to their target sites, where cell?Ccell adhesion enables them to aggregate and form tissues. Here, we extend analysis of the model of cell migration proposed by Anguige and Schmeiser (J. Math. Biol. 58(3):395?C427, 2009) that incorporates both cell?Ccell adhesion and volume filling. The stochastic space-jump model is compared to two deterministic counterparts (a system of stochastic mean equations and a non-linear partial differential equation), and it is shown that the results of the deterministic systems are, in general, qualitatively similar to the mean behaviour of multiple stochastic simulations. However, individual stochastic simulations can give rise to behaviour that varies significantly from that of the mean. In particular, individual simulations might admit cell clustering when the mean behaviour does not. We also investigate the potential of this model to display behaviour predicted by the differential adhesion hypothesis by incorporating a second cell species, and present a novel approach for implementing models of cell migration on a growing domain.     

黏附分子在肿瘤发生及发展中的作用

细胞黏附分子是以配体和受体相结合的形式,介导细胞与细胞间或细胞与基质间相互作用的一类分子,参与机体的多种重要生理和病理过程.近年来,在对肿瘤发生和发展的研究中发现,黏附分子可通过多种途径影响肿瘤的生长、浸润及转移过程.因此.对黏附分子在肿瘤发生和发展中作用及机制的深入研究,可为肿瘤早期诊断提供重要的分子指标和发现新的治疗靶标.并为进而形成临床诊疗新策略提供重要理论支持.现就几种重要黏附分子在肿瘤生长与转移中的作用进行综述.     

IgLON Cell Adhesion Molecules Are Shed from the Cell Surface of Cortical Neurons to Promote Neuronal Growth

Matrix metalloproteinases and a disintegrin and metalloproteinases are members of the zinc endopeptidases, which cleave components of the extracellular matrix as well as cell surface proteins resulting in degradation or release of biologically active fragments. Surface ectodomain shedding affects numerous biological processes, including survival, axon outgrowth, axon guidance, and synaptogenesis. In this study, we evaluated the role of metalloproteinases in regulating cortical neurite growth. We found that treatment of mature cortical neurons with pan-metalloproteinase inhibitors or with tissue inhibitors of metalloproteinase-3 reduced neurite outgrowth. Through mass spectrometry, we characterized the metalloproteinase-sensitive cell surface proteome of mature cortical neurons. Members of the IgLON family of glycosylphosphatidylinositol-anchored neural cell adhesion molecules were identified and validated as proteins that were shed from the surface of mature cortical neurons in a metalloproteinase-dependent manner. Introduction of two members of the IgLON family, neurotrimin and NEGR1, in early embryonic neurons was sufficient to confer sensitivity to metalloproteinase inhibitors in neurite outgrowth assays. Outgrowth experiments on immobilized IgLON proteins revealed a role for all IgLON family members in promoting neurite extension from cortical neurons. Together, our findings support a role for metalloproteinase-dependent shedding of IgLON family members in regulating neurite outgrowth from mature cortical neurons.     

神经细胞粘附分子与记忆

记忆的形成阶段包含着神经元突触的可塑性变化过程.近年来的研究表明,神经细胞粘附分子可同时增进突触的可塑性和维持突触结构的稳定性.许多研究证实神经细胞粘附分子对与学习和记忆相关的过程起着一定的调节作用.     

盘基网柄菌细胞的粘附分子

盘基网柄菌（Dictyostelium discoideum)依赖4种类型细胞粘附系统的表达使其多细胞发育顺利进行。在发育初期,由钙结合蛋白DdCAD-1调节EDTA／EGTA敏感的粘着位点。在发育的多细胞聚集阶段,出现EDTA抗性的粘着位点,由分子是80kD蛋白（gp80)通过同嗜性粘着的相互作用末调节细胞的粘着,它的细胞结合位点是一个八肽序列。由分子量150kD蛋白（gp150)通过异嗜性粘着的相互作用来调节多细胞后聚集的细胞粘着。本文详细讨论了gp80和gp150调节细胞粘着的机制。     

黏着斑激酶与细胞迁移

细胞迁移过程始于细胞前端板状伪足的形成、外周黏附的建立、细胞体的收缩和尾部的解离.黏着斑激酶是一种非受体酪氨酸蛋白激酶,通过其激酶活性和"脚手架"的功能在细胞迁移的各个过程中发挥关键作用.现重点介绍黏着斑激酶介导的信号转导通路及其在调控细胞迁移方面的研究进展.     

Good Time for Cell Adhesion and Migration

Our understanding of the molecular and cellular mechanisms controlling cell adhesion and migration has never been so high. The era of “molecular interactions” requires an appropriate tool for exchanging views, presenting outstanding results and discussing new concepts in the field. This is why we decided to launch Cell Adhesion and Migration (CAM), a multi-disciplinary journal publishing original research articles and reviews covering the latest aspects of cellular and molecular mechanisms and their regulation both during physiological and pathological processes.     

Cytokines and Cell Adhesion Molecules in Tumor-Endothelial Cell Interaction and Metastasis

Metastasis is a multistep process in which a metastatic tumor cell detaches from the primary tumor, invades the surrounding tissues, passes through supporting structures such as interstitial stroma and extracellular matrix, and enters the lymphatic or blood circulation (Poste and Fidler, 1980). Only a few of the neoplastic cells released into the circulation, that survive hemodynamic pressure and host defense mechanisms, will form metastases. The arrest of tumor cells in the capillary bed of secondary organs through an interaction with vascular or lymphatic endothelium and subendothelial basement membrane is followed by their extravasation into the tissue parenchyma, and then micro-metastasis formation. Therefore cell-cell and cell-substrate adhesions occur at different moments in this process. With the recent identification and characterization of cell surface molecules, it has become of particular interest to clarify their role in tumor progression and metastasis (Albelda, 1993).     

Cytokines and Cell Adhesion Molecules in Tumor-Endothelial Cell Interaction and Metastasis

Metastasis is a multistep process in which a metastatic tumor cell detaches from the primary tumor, invades the surrounding tissues, passes through supporting structures such as interstitial stroma and extracellular matrix, and enters the lymphatic or blood circulation (Poste and Fidler, 1980). Only a few of the neoplastic cells released into the circulation, that survive hemodynamic pressure and host defense mechanisms, will form metastases. The arrest of tumor cells in the capillary bed of secondary organs through an interaction with vascular or lymphatic endothelium and subendothelial basement membrane is followed by their extravasation into the tissue parenchyma, and then micro-metastasis formation. Therefore cell-cell and cell-substrate adhesions occur at different moments in this process. With the recent identification and characterization of cell surface molecules, it has become of particular interest to clarify their role in tumor progression and metastasis (Albelda, 1993).     

Neuronal Pathfinding and Recognition: Roles of Cell Adhesion Molecules

Neurons contact their neighbors through a diverse array of cell adhesion and other surface molecules. These molecules can exhibit highly regulated patterns of expression, underscoring their multiple roles in establishing specific interactions between neurons and their environment. Recent studies are beginning to ask how these membrane-bound neural recognition molecules interact with each other and intracellular signaling pathways within an individual neuronal growth cone, and direct the formation of neural connections during development.     

Expression of Endothelial Cell Adhesion Molecules in Joints and Heart during Borrelia burgdorferi Infection of Mice

The expression of adhesion molecules on endothelia was examined during chronic arthritis and carditis in SCID and immunocompetent susceptible AKR/N mice infected with Borrelia burgdorferi (B. burgdorferi). All stages of disease were associated with the upregulation or new expression of ICAM-1 and P-selectin and of VCAM-1 and E-selectin, respectively, on blood vessels of affected joint tissues of SCID and AKR/N mice as well as on heart tissue of SCID mice but not in other tissues. Moreover, ICAM-1 was also found on infiltrating mononuclear cells. The overall staining intensity for each of the four adhesion molecules on individual tissue sections of joint and heart increased with time of infection and was associated with the presence of spirochetes in the tissue. In addition it is shown that in both mouse strains inflammation of joints but not heart is accompanied by vascular proliferation. Synovial but not heart tissues of infected SCID mice were found to express both, peripheral-(PNAd) and mucosal (MAdCAM-1) lymph node high endothelia venule associated vascular addressins as detected by mAb Meca-79 and Meca-367, respectively, but only at later stages of the disease and only on newly generated small venules. However, neither of the two addressins were evident in synovial lesions of AKR/N mice. Together the data suggest that the concomittant induction of ICAM-1, VCAM-1, E-selectin and P-selectin in lesions of infected mice provide a means for enhanced cellular infiltration into affected organs and that the regulation of these structures is conserved in the absence of a functional immune system. Furthermore, the differential induction of vascular proliferation in joint and heart tissues as well as the restricted expression patterns of vascular addressins indicate that the pathogenetic processes induced by B. burgdorferi are distinct for joint and heart.     

EphB/ephrinB Signaling in Cell Adhesion and Migration

Eph receptors and their ligands, ephrins, represent the largest group of the receptor tyrosine kinase (RTK) family, and they mediate numerous developmental processes in a variety of organisms. Ephrins are membrane-bound proteins that are mainly divided into two classes: A class ephrins, which are linked to the membrane by a glycosylphosphatidylinositol (GPI) linkage, and B class ephrins, which are transmembrane ligands. Based on their domain structures and affinities for ligand binding, the Eph receptors are also divided into two groups. Trans-dimerization of Eph receptors with their membrane-tethered ligands regulates cell-cell interactions and initiates bidirectional signaling pathways. These pathways are intimately involved in regulating cytoskeleton dynamics, cell migration, and alterations in cellular dynamics and shapes. The EphBs and ephrinBs are specifically localized and modified to promote higher-order clustering and initiate of bidirectional signaling. In this review, we present an in-depth overview of the structure, mechanisms, cell signaling, and functions of EphB/ephrinB in cell adhesion and migration.     

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

Cell-cell adhesion is fundamental to multicellular life and is mediated by a diverse array of cell surface proteins. However, the adhesive interactions for many of these proteins are poorly understood. Here we present a simple, rapid method for characterizing the adhesive properties of putative homophilic cell adhesion molecules. Cultured HEK293 cells are transfected with DNA plasmid encoding a secreted, epitope-tagged ectodomain of a cell surface protein. Using functionalized beads specific for the epitope tag, the soluble, secreted fusion protein is captured from the culture medium. The coated beads can then be used directly in bead aggregation assays or in fluorescent bead sorting assays to test for homophilic adhesion. If desired, mutagenesis can then be used to elucidate the specific amino acids or domains required for adhesion. This assay requires only small amounts of expressed protein, does not require the production of stable cell lines, and can be accomplished in 4 days.     

Recombinant Human Collagen XV Regulates Cell Adhesion and Migration

The C-terminal end of collagen XV, restin, has been the focus of several studies, but the functions of full-length collagen XV have remained unknown. We describe here studies on the production, purification, and function of collagen XV and the production of a monoclonal N-terminal antibody to it. Full-length human collagen XV was produced in insect cells using baculoviruses and purified from the cell culture medium. The yield was 15 mg/liter of cell culture medium. The collagen XV was shown to be trimeric, with disulfide bonds in the collagenous region. Rotary shadowing electron microscopy revealed rod-like molecules with a mean length of 241.8 nm and with a globular domain at one end. The globular domain was verified to be the N-terminal end by N-terminal antibody binding. The molecules show flexibility in their conformation, presumably due to the many interruptions in their collagenous domains. The ability of collagen XV to serve as a substrate for cells was tested in cell adhesion assays, and it was shown that cells did not bind to collagen XV-coated surfaces. When added to the culture medium of fibroblasts and fibrosarcoma cells, however, collagen XV rapidly bound to their fibronectin network. Solid phase assays showed that collagen XV binds to fibronectin, laminin, and vitronectin and that it binds to the collagen/gelatin-binding domain of fibronectin. No binding was detected to fibrillar collagens, fibril-associated collagens, or decorin. Interestingly, collagen XV was found to inhibit the adhesion and migration of fibrosarcoma cells when present in fibronectin-containing matrices.