Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion

Bardin, Nathalie; Anfosso, Francine; Massé, Jean‐Marc; Cramer, Elisabeth M.; Sabatier, Florence; Bivic, André Le; Sampol, José; Dignat-George, Françoise

doi:10.1182/blood.v98.13.3677

Cited by 269 publications

(258 citation statements)

References 39 publications

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“…Specificity of purified AMM-1 and AMM-2 was evaluated by their binding to B16 cells, murine endothelial bEnd2 cells (a gift from Dr. M. Aurrand-Lions) and mouse L929 fibroblasts [11]. Rat preimmune serum and rat IgG1 purchased from BD Biosciences were used as controls.…”

Section: Immunogen and Hybridomasmentioning

confidence: 99%

“…Hybridoma screening was performed by flow cytometry analysis using FC500 cytometer (Beckmann Coulter) after staining of B16 melanoma cells with hybridoma supernatants. Specificity of purified AMM-1 and AMM-2 was evaluated by their binding to B16 cells, murine endothelial bEnd2 cells (a gift from Dr. M. Aurrand-Lions) and mouse L929 fibroblasts [11]. Rat preimmune serum and rat IgG1 purchased from BD Biosciences were used as controls.…”

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confidence: 99%

“…Using S-Endo1 mAb, we previously detected cell surface expression of CD146 on human vascular endothelial cells, whatever vessel caliber or anatomical region [10]. On cultured endothelial cells, CD146 is mainly located at the intercellular junctions and is involved in inter-endothelial cell adhesion and paracellular permeability [11,12]. CD146 cross-linking in HUVEC induces a tyrosine phosphorylation of the non-receptor tyrosine kinase p59 fyn , of focal adhesion kinase and of paxillin, suggesting a role of CD146 in the reorganization of the cytoskeleton [13,14].…”

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confidence: 99%

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Mouse CD146/MCAM is a marker of natural killer cell maturation

et al. 2008

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CD146/melanoma cell adhesion molecule is an adhesion molecule expressed by endothelial cells and by a small fraction of activated T and B lymphocytes in humans. In order to analyze the pattern of CD146 expression in mouse leukocytes at steady-state conditions, we generated a set of novel rat anti-mouse CD146 monoclonal antibodies. CD146 expression was undetectable on monocytes, dendritic cells, T cells or B cells, but was expressed on about 30% of neutrophils and 60% of NK cells. Within murine lymphocytes, CD146 was defined as a novel NK-specific surface molecule. An increased percentage of CD146 1 cells was found in the most mature CD27 À CD11b 1 NK cell subpopulation, which also displays higher expression of Ly49C/I, Ly49D and KLRG1 and lower expression of NKG2A/C/E molecules. CD146 1 NK cells were found to be less cytotoxic and produce less IFN-c than CD146 À NK cells upon stimulation with target cells or activating antibodies. These findings define CD146 as a marker of mouse NK cell maturation that may be used as an alternative to the combined use of CD27 and CD11b staining to detect final stages of NK cell maturation.Key words: Adhesion . Antibodies . CD146/MCAM . Maturation . NK cells Introduction CD146, also known as melanoma cell adhesion molecule (MCAM or Mel-CAM), MUC18, S-Endo1, A32 antigen, is an integral membrane glycoprotein of 113 kDa that belongs to the Ig superfamily with a characteristic V-V-C2-C2-C2 domain structure [1]. Two others members of this family have been identified in humans: basal-cell adhesion molecule and activated leukocytecell adhesion molecule, also called CD166 [2,3]. Basal-cell adhesion molecule is a splice variant of the Lutheran blood group glycoprotein that is reported to bind laminin [3]. Activated leukocyte-cell adhesion molecule is a costimulatory molecule mediating homophilic interaction and heterophilic interaction with CD6 and is involved in activation and trafficking of leukocytes into the central nervous system [4]. CD146 was originally defined as a marker of tumor progression and metastasis formation in human melanoma [5]. Overexpression of CD146 in CD146-negative melanoma cells renders these cells highly metastatic after injection in immunodeficient mice [6]. Moreover, injection of a humanized anti-CD146 mAb in immunodeficient mice bearing human melanomas significantly reduces the tumor size and the number of metastases [7]. The adhesive functions of CD146 were demonstrated using a solid-phase adhesion test in which both CD146-positive and CD146-negative melanoma cells bound to eucaryotic recombinant CD146 protein, suggesting that CD146 can mediate both homophilic and heterophilic interaction with an as yet unidentified ligand [8,9]. Using S-Endo1 mAb, we previously detected cell surface expression of CD146 on human vascular endothelial cells, whatever vessel caliber or anatomical region [10]. On cultured endothelial cells, CD146 is mainly located at the intercellular junctions and is involved in inter-endothelial cell adhesion and paracellular permeability [11,1...

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Section: Immunogen and Hybridomasmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Mouse CD146/MCAM is a marker of natural killer cell maturation

et al. 2008

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“…The typical transmembrane protein in adherens junctions is vascular endothelial (VE ) cadherin, while occludin and members of the claudin family are present in tight junctions (Dejana, 2004). In addition, other adhesive molecules are localized outside these structures, for example, platelet endothelial cell adhesion molecule 1 (PECAM 1, CD31) and CD146 (Dejana, 2004;Bardin et al, 2001). CD146 (also referred to as MUC18, MCAM, Mel CAM, S Endo 1, P1H12 antigen) was initially identified as a marker of tumor progression and metastasis formation in human melanoma (Lehmann et al, 1989;Shih et al, 1997a;Bardin et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Soluble CD146 is generated by ectodomain shedding of membrane CD146 in a calcium-induced, matrix metalloprotease-dependent process

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Legler

et al. 2009

Microvascular Research

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CD146 is a cell adhesion molecule localized at the endothelial junction and is involved in the control of cell cell cohesion. In this study, we showed that calcium influx in human microvascular lung endothelial cells results in the loss of surface CD146 and the release of soluble CD146. This calcium induced CD146 shedding could be prevented with inhibitors of matrix metalloproteases indicating a central role of matrix metalloproteases in this process. We also investigated if CD146 shedding influences vascular permeability. Endothelial cell monolayers cultured on filter membranes showed an increased permeability for albumin when stimulated with ionomycin. This calcium induced increase in permeability was inhibited when CD146 shedding was prevented by a matrix metalloprotease inhibitor. Our data indicate that surface CD146 plays a central role in the regulation of vascular permeability and demonstrate that CD146 and matrix metalloproteases are potential targets to modify endothelial barrier function.

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“…In order to better evaluate in vivo perifosine effects on TECs, tumor nodules from mice receiving control vehicle or perifosine were collected and homogenized to obtain a cell suspension. As CD146 is widely expressed by murine endothelial cells [45,46] and by the endothelium of both SU-DHL-4V and KMS-11 tumor models (Fig. 3a), TECs were efficiently separated from tumor cells by immunomagnetic sorting using a magnetic bead-conjugated anti-mouse CD146 antibody (Fig.…”

Section: Perifosine Inhibits In Vivo Akt Phosphorylation Both In Tumomentioning

confidence: 99%

Induction of death receptor 5 expression in tumor vasculature by perifosine restores the vascular disruption activity of TRAIL-expressing CD34+ cells

et al. 2013

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The proapoptotic death receptor 5 (DR5) expressed by tumor associated endothelial cells (TECs) mediates vascular disrupting effects of human CD34 ? cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL 1 cells) in mice. Indeed, lack of DR5 on TECs causes resistance to CD34-TRAIL 1 cells. By xenografting in nonobese diabetic/severe combined immunodeficient mice the TRAIL-resistant lymphoma cell line SU-DHL-4V, which generates tumors lacking endothelial DR5 expression, here we demonstrate for the first time that the Akt inhibitor perifosine induces in vivo DR5 expression on TECs, thereby overcoming tumor resistance to the vascular disruption activity of CD34-TRAIL 1 cells. In fact, CD34-TRAIL 1 cells combined with perifosine, but not CD34-TRAIL 1 cells alone, exerted marked antivascular effects and caused a threefold increase of hemorrhagic necrosis in SU-DHL-4V tumors. Consistent with lack of DR5 expression, CD34-TRAIL 1 cells failed to affect the growth of SU-DHL-4V tumors, but CD34-TRAIL 1 cells plus perifosine reduced tumor volumes by 60 % compared with controls. In view of future clinical studies using membrane-bound TRAIL, our results highlight a strategy to rescue patients with primary or acquired resistance due to the lack of DR5 expression in tumor vasculature.

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Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion

Cited by 269 publications

References 39 publications

Mouse CD146/MCAM is a marker of natural killer cell maturation

Mouse CD146/MCAM is a marker of natural killer cell maturation

Soluble CD146 is generated by ectodomain shedding of membrane CD146 in a calcium-induced, matrix metalloprotease-dependent process

Induction of death receptor 5 expression in tumor vasculature by perifosine restores the vascular disruption activity of TRAIL-expressing CD34+ cells

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