Outside-in Signaling Pathway Linked to CD146 Engagement in Human Endothelial Cells

Anfosso, Francine; Bardin, Nathalie; Vivier, Éric; Sabatier, Florence; Sampol, José; Dignat-George, Françoise

doi:10.1074/jbc.m007065200

Cited by 124 publications

(122 citation statements)

References 60 publications

(50 reference statements)

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“…The intracellular domain promotes the recruitment of the Src family kinase FYN as well as tyrosine phosphorylation of several intracellular proteins, including FAK (and paxillin), that are present in focal adhesion plaques. 37,50,51 We observed increased FAK and FYN immunostaining in breast carcinomas of poor outcome compared with tumors from patients with longer survival. This is probably a result of increased cellular signals from cMet and CD146, which both act through FYN signaling pathways upon angiogenesis and rearrangement of the actin skeleton.…”

Section: Discussionmentioning

confidence: 60%

“…This is probably a result of increased cellular signals from cMet and CD146, which both act through FYN signaling pathways upon angiogenesis and rearrangement of the actin skeleton. [49][50][51] Experimental studies have shown that anti-CD146 monoclonal antibodies inhibit proliferation and migration of endothelial cells and angiogenesis, reflected by a reduction in blood vessel density associated with tumor growth inhibition. 51 This treatment exhibited no cytotoxic effects in animals, and its efficacy increased when the anti-CD146 monoclonal antibody AA98 was combined with other anticancer agents.…”

Section: Discussionmentioning

confidence: 99%

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A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Charpin

Secq

Giusiano

et al. 2009

Intl Journal of Cancer

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Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow‐up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c‐Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c‐erb B2), and 15 when ER, PgR and c‐erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost‐effective. Quantitative densitometric measurement of immunoprecipitates by computer‐assisted devices from digitized microscopic images allows standardized high‐throughput “in situ” molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies. © 2008 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Charpin

Secq

Giusiano

et al. 2009

Intl Journal of Cancer

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“…MCAM can mediate homophilic cell-cell adhesion, as well as heterophilic adhesions, through interaction with an unknown ligand. MCAM has been shown to activate intracellular signaling pathways and to regulate cell growth (32,33). MCAM inhibition attenuated tumor growth and metastasis by inhibition of interaction between melanoma cells and endothelial cells (34,35).…”

Section: Discussionmentioning

confidence: 99%

Targeted Disruption of Endothelial Cell-selective Adhesion Molecule Inhibits Angiogenic Processes in Vitro and in Vivo

Ishida

Kundu

Yang

et al. 2003

Journal of Biological Chemistry

103

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“…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]. Several lines of evidence from the literature point out a role of CD146 in vascular development.…”

mentioning

confidence: 99%

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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Outside-in Signaling Pathway Linked to CD146 Engagement in Human Endothelial Cells

Cited by 124 publications

References 60 publications

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Targeted Disruption of Endothelial Cell-selective Adhesion Molecule Inhibits Angiogenic Processes in Vitro and in Vivo

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

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