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32-470: 84004 ENSG00000076706 ENSMUSG00000032135 P43121 Q8R2Y2 NM_006500 NM_023061 NM_001359530 NP_006491 NP_075548 NP_001346459 CD146 ( cluster of differentiation 146) also known as the melanoma cell adhesion molecule ( MCAM ) or cell surface glycoprotein MUC18 , is a 113kDa cell adhesion molecule currently used as a marker for endothelial cell lineage. In humans,
64-410: A chemokine receptor on the surface of a T helper cell to gain entry. The number of CD4 and CD8 T cells in blood is often used to monitor the progression of HIV infection . While CD molecules are very useful in defining leukocytes, they are not merely markers on the cell surface . Though only a fraction of known CD molecules have been thoroughly characterised, most of them have important functions. In
96-578: A stem cell , as opposed to a fully differentiated endothelial cell . Some cell populations can also be defined as , , or (alternatively, , , or ), indicating an overall variability in CD expression , particularly when compared to other cells being studied. A review of the development of T cells in the thymus uses this nomenclature to identify cells transitioning from CD4 /CD8 double-positive cells to CD4 /CD8 . Since 1982 there have been nine Human Leukocyte Differentiation Antigen Workshops culminating in
128-409: A class of CAMs. One classification system involves the distinction between calcium-independent CAMs and calcium-dependent CAMs. The Ig-superfamily CAMs do not depend on Ca while integrins, cadherins and selectins depend on Ca . In addition, integrins participate in cell–matrix interactions, while other CAM families participate in cell–cell interactions. Immunoglobulin superfamily CAMs (IgSF CAMs)
160-426: A conference. The CD system is commonly used as cell markers in immunophenotyping , allowing cells to be defined based on what molecules are present on their surface. These markers are often used to associate cells with certain immune functions . While using one CD molecule to define populations is uncommon (though a few examples exist), combining markers has allowed for cell types with very specific definitions within
192-438: A crucial role in orchestrating circulating lymphocytes. CAM function in cancer metastasis, inflammation, and thrombosis makes it a viable therapeutic target that is currently being considered. For example, they block the metastatic cancer cells' ability to extravasate and home to secondary sites. This has been successfully demonstrated in metastatic melanoma that hones to the lungs. In mice, when antibodies directed against CAMs in
224-581: A subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion . In essence, CAMs help cells stick to each other and to their surroundings. CAMs are crucial components in maintaining tissue structure and function. In fully developed animals, these molecules play an integral role in generating force and movement and consequently ensuring that organs are able to execute their functions normally. In addition to serving as "molecular glue", CAMs play important roles in
256-422: Is regarded as the most diverse superfamily of CAMs. This family is characterized by their extracellular domains containing Ig-like domains. The Ig domains are then followed by Fibronectin type III domain repeats and IgSFs are anchored to the membrane by a GPI moiety. This family is involved in both homophilic or heterophilic binding and has the ability to bind integrins or different IgSF CAMs. Integrins , one of
288-522: Is through homophilic binding, where CAMs bind with the same CAMs. They are also capable of heterophilic binding, meaning a CAM on one cell will bind with different CAMs on another cell. There are four major superfamilies or groups of CAMs: the immunoglobulin super family of cell adhesion molecules ( IgCAMs ), Cadherins , Integrins , and the Superfamily of C-type of lectin-like domains proteins ( CTLDs ). Proteoglycans are also considered to be
320-568: The CAMS that are particularly important in the lymphocyte homing is addressin . Lymphocyte homing is a key process occurring in a strong immune system. It controls the process of circulating lymphocytes adhering to particular regions and organs of the body. The process is highly regulated by cell adhesion molecules, particularly, the addressin also known as MADCAM1. This antigen is known for its role in tissue-specific adhesion of lymphocytes to high endothelium venules. Through these interactions they play
352-523: The CD146 protein is encoded by the MCAM gene . MCAM functions as a receptor for laminin alpha 4, a matrix molecule that is broadly expressed within the vascular wall. Accordingly, MCAM is highly expressed by cells that are components of the blood vessel wall, including vascular endothelial cells, smooth muscle cells and pericytes. Its function is still poorly understood, but evidence points to it being part of
SECTION 10
#1732779529506384-453: The ECDs are necessary for cell adhesion . The cytoplasmic domain has specific regions where catenin proteins bind. The selectins are a family of heterophilic CAMs that are dependent on fucosylated carbohydrates, e.g., mucins for binding. The three family members are E-selectin ( endothelial ), L-selectin ( leukocyte ), and P-selectin ( platelet ). The best-characterized ligand for
416-453: The alpha and beta subunits there is a large extracellular domain, a transmembrane domain and a short cytoplasmic domain. The extracellular domain is where the ligand binds through the use of divalent cations . The integrins contain multiple divalent cation binding sites in the extracellular domain ). The integrin cation binding sites can be occupied by Ca2+ or by Mn2+ ions. Cations are necessary but not sufficient for integrins to convert from
448-442: The cell surface. MCAM inhibits breast cancer progression. Normal melanocytes do not express MCAM and the expression of MCAM is first found in nevi and melanoma cells. MCAM expression is positively correlated to melanoma progression at which the expression of MCAM is highest in metastatic melanoma cells. The significance of MCAM upregulation is evident in melanoma cells cultured in 3D skin reconstruct in which MCAM facilitates
480-536: The cell. A signal cascade is usually initiated, altering the behavior of the cell (see cell signaling ). Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion . CD for humans is numbered up to 371 (as of 21 April 2016 ). The CD nomenclature was proposed and established in the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Paris in 1982. This system
512-472: The cellular mechanisms of growth, contact inhibition, and apoptosis. Aberrant expression of CAMs may result in a wide range of pathologies, ranging from frostbite to cancer. CAMs are typically single-pass transmembrane receptors and are composed of three conserved domains: an intracellular domain that interacts with the cytoskeleton , a transmembrane domain, and an extracellular domain. These proteins can interact in several different ways. The first method
544-426: The designation (e.g., CD2 molecule). Currently, "CD2" is generally used to designate the molecule, and "CD2 antibody " is used to designate the antibody. Cell populations are usually defined using a '+' or a '−' symbol to indicate whether a certain cell fraction expresses or lacks a CD molecule. For example, a " CD34 +, CD31 −" cell is one that expresses CD34 but not CD31. This CD combination typically corresponds to
576-571: The endothelial junction associated with the actin cytoskeleton. A member of the Immunoglobulin superfamily , it consists of five Ig domains, a transmembrane domain, and a cytoplasmic region. It is expressed on chicken embryonic spleen and thymus, activated human T cells, endothelial progenitors such as angioblasts and mesenchymal stem cells , and strongly expressed on blood vessel endothelium and smooth muscle. Two isoforms exist (MCAM long (MCAM-1), and MCAM short, or MCAM-s) which differ in
608-451: The example of CD4 and CD8, these molecules are critical in antigen recognition. Others (e.g., CD135 ) act as cell surface receptors for growth factors . Recently, the marker CD47 was found to have anti- phagocytic signals to macrophages and inhibit natural killer (NK) cells. This enabled researchers to apply CD47 as a potential target to attenuate immune rejection . Cell surface molecule Cell adhesion molecules ( CAMs ) are
640-474: The expression of MCAM on melanoma cells. Cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD ) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to
672-842: The formation of the mesoderm , endoderm , and ectoderm . Cadherins also contribute significantly to the development of the nervous system. The distinct temporal and spatial localization of cadherins implicates these molecules as major players in the process of synaptic stabilization . Each cadherin exhibits a unique pattern of tissue distribution that is carefully controlled by calcium. The diverse family of cadherins include epithelial (E-cadherins), placental (P-cadherins), neural (N-cadherins), retinal ( R-cadherins ), brain (B-cadherins and T-cadherins), and muscle (M-cadherins). Many cell types express combinations of cadherin types. The extracellular domain has major repeats called extracellular cadherin domains (ECD). Sequences involved in Ca binding between
SECTION 20
#1732779529506704-509: The immune system. CD molecules are utilized in cell sorting using various methods, including flow cytometry . Two commonly used CD molecules are CD4 and CD8 , which are, in general, used as markers for helper and cytotoxic T cells, respectively. These molecules are defined in combination with CD3+, as some other leukocytes also express these CD molecules (some macrophages express low levels of CD4; dendritic cells express high levels of CD8). Human immunodeficiency virus binds CD4 and
736-553: The inactive bent conformation into the active extended conformation. Both the presence of cations bound to the multiple cation binding sites is required, along with the direct physical association with ECM ligands for integrins to attain the extended structure and concomitant activation. Thus, rise in extracellular Ca2+ ions may serve to prime the integrin heterodimer. The release of intracellular Ca2+ have been shown to be important for integrin inside-out activation. However, extracellular Ca2+ binding may exert different effects depending on
768-675: The inflammatory response. CD146 has been demonstrated to appear on a small subset of T and B lymphocytes in the peripheral blood of healthy individuals. The CD146+ T cells display an immunophenotype consistent with effector memory cells and have a distinct gene profile from the CD146- T cells. CD146 T cells have been shown by Dagur and colleagues to produce IL-17. CD146 has been seen as a marker for mesenchymal stem cells isolated from multiple adult and fetal organs, and its expression may be linked to multipotency; mesenchymal stem cells with greater differentiation potential express higher levels of CD146 on
800-498: The integrin into its high affinity state, which causes increased fibrinogen binding, causing platelet aggregation. The cadherins are homophilic Ca -dependent glycoproteins . The classic cadherins ( E- , N- and P- ) are concentrated at the intermediate cell junctions , which link to the actin filament network through specific linking proteins called catenins . Cadherins are notable in embryonic development. For example, cadherins are crucial in gastrulation for
832-489: The length of their cytoplasmic domain. Activation of these isoforms seems to produce functional differences as well. Natural killer cells transfected with MCAM-1 demonstrate decreased rolling velocity and increased cell adhesion to an endothelial cell monolayer and increased microvilli formation while cells transfected with MCAM-s showed no change in adhesion characteristics. Since these characteristics are important in leukocyte extravasation , MCAM-1 may be an important part of
864-639: The major classes of receptors within the ECM, mediate cell–ECM interactions with collagen , fibrinogen , fibronectin , and vitronectin . Integrins provide essential links between the extracellular environment and the intracellular signalling pathways, which can play roles in cell behaviours such as apoptosis , differentiation , survival , and transcription . Integrins are heterodimeric , as they consist of an alpha and beta subunit. There are currently 18 alpha subunits and 8 beta subunits, which combine to make up 24 different integrin combinations. Within each of
896-448: The migration of melanoma into the dermis . Without the expression of MCAM melanoma cells are controlled by keratinocytes in the epidermis that inhibit penetrance beyond the basement membrane . The control by keratinocytes are only achieved by E-cadherin expression on the surface of melanoma cells. Melanoma cells with functional E-cadherin on the surface can only exclusively grow in the epidermis as keratinocytes frequently downregulate
928-409: The molecule. If the molecule has not been well characterized or has only one mAb, it is usually given the provisional indicator "w" (as in " CDw186 "). For instance, CD2 mAbs are reagents that react with a 50‐kDa transmembrane glycoprotein expressed on T cells . The CD designations were used to describe the recognized molecules but had to be clarified by attaching the term antigen or molecule to
960-450: The three selectins is P-selectin glycoprotein ligand-1 ( PSGL-1 ), which is a mucin-type glycoprotein expressed on all white blood cells. Selectins have been implicated in several roles but they are especially important in the immune system by helping white blood cell homing and trafficking. The variety in CAMs leads to diverse functionality of these proteins in the biological setting. One of
992-432: The type of integrin and the cation concentration. Integrins regulate their activity within the body by changing conformation. Most exist at rest in a low affinity state, which can be altered to high affinity through an external agonist which causes a conformational change within the integrin, increasing their affinity. An example of this is the aggregation of platelets ; Agonists such as thrombin or collagen trigger
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1024-461: Was intended for the classification of the many monoclonal antibodies (mAbs) generated by different laboratories around the world against epitopes on the surface molecules of leukocytes (white blood cells). Since then, its use has expanded to many other cell types, and more than 370 CD unique clusters and subclusters have been identified. The proposed surface molecule is assigned a CD number once two specific monoclonal antibodies are shown to bind to
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