The Involvement of CD146 and Its Novel Ligand Galectin-1 in Apoptotic Regulation of Endothelial Cells

Jouve, Nathalie; Despoix, Nicolas; Espéli, Marion; Gauthier, Laurent; Cypowyj, Sophie; Fallague, Karim; Schiff, Claudine; Dignat-George, Françoise; Vély, Frederic; Leroyer, Aurélie S.

doi:10.1074/jbc.m112.418848

Cited by 62 publications

(49 citation statements)

References 62 publications

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“…In the current study, Gal-1-induced apoptosis of eosinophils did not appear to involve activation of caspases, similar to the effects observed in endothelial cells (24). However, a role for ERK(1/2) was identified.…”

Section: Discussionsupporting

confidence: 51%

“…The proapoptotic effect of Gal-1 has previously been demonstrated in other cell types such as T cells (14), B cells (22), epithelial cells (23), and endothelial cells (24) but not macrophages, DCs, or mast cells (25). Gal-1-induced apoptosis of both BM-derived as well as peripheral blood eosinophils from allergen-challenged mice occurred at lower concentrations and more rapidly (≥1 μM by 15 min) than in T cells (14), B cells (22), and endothelial cells (24). Further, Gal-1 treatment caused cell shrinkage in eosinophils, a hallmark feature of apoptosis (26).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Greenberg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1–expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan– and dose-dependent. At concentrations ≤0.25 µM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1–induced migration. Exposure to concentrations ≥1 µM resulted in ERK(1/2)-dependent apoptosis and disruption of the F-actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1–deficient mice exhibited increased recruitment of eosinophils and CD3+ T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Greenberg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Further EVT-specific genes and other highly expressed genes are listed in Tables 1 and 2 and discussed in the Supplemental Material. These cells differ from cytotrophoblasts by expression of some endothelial genes, such as adhesion molecule MCAM (Jouve et al 2013;Kaspi et al 2013), lowered E-cadherin (CDH1) (Zhou et al 1997), and the receptor for vascular endothelial growth factor FLT1. Note that MCAM may be a receptor for WNT5A, affecting cell motility (Ye et al 2013).…”

Section: Extravillous Trophoblast (Evt; Cluster 5)mentioning

confidence: 99%

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

et al. 2017

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Organismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome by assessing the gene expression of receptor-ligand pairs across cell types. We find a highly cell-type-specific expression of G-protein-coupled receptors, implying that ligand-receptor profiles could be a reliable tool for cell type identification. Furthermore, we find that uterine decidual cells represent a cell-cell interaction hub with a large number of potential incoming and outgoing signals. Decidual cells differentiate from their precursors, the endometrial stromal fibroblasts, during uterine preparation for pregnancy. We show that decidualization (even in vitro) enhances the ability to communicate with the fetus, as most of the receptors and ligands up-regulated during decidualization have their counterpart expressed in trophoblast cells. Among the signals transmitted, growth factors and immune signals dominate, and suggest a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene expression profiles of term intravillous and extravillous trophoblasts, including the transcriptome of the multinucleated syncytiotrophoblast.

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“…Binding of Netrin-1 to CD146/MCAM was reported to activate an array of downstream signaling and increase endothelial cell proliferation, migration, and angiogenesis (29). Recently, CD146 was reported to interact with exogenously introduced galectin-1 in endothelial cells and protects against galectin-1-induced cell apoptosis (30). Endogenous galectin-3 expression in HUVECs was found to be low (Fig.…”

Section: Galectin-3-cd146 Interaction Induces Cytokine Secretionmentioning

confidence: 99%

Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells

Colomb

Wang

Simpson

et al. 2017

Journal of Biological Chemistry

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The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines. Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling. siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells. Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines. We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.Galectin-3 is a galactoside-binding protein that is expressed by many types of human cells. Overexpression of galectin-3 commonly occurs in most types of cancer (1, 2) and is increasingly recognized to influence cancer cell-cell and cancer-microenvironment communications and contributes to cancer development, progression, and metastasis as a result of galectin-3 interaction with various galactose-terminated glycans carried on the cell surface and in the extracellular matrix (2).Earlier studies by us as well as by other groups have revealed that the concentration of circulating galectin-3 is markedly increased, up to 30-fold, in the bloodstream of cancer patients, including those with colorectal, breast, lung, bladder, pancreatic, and head and neck cancers and melanoma (2-8). Patients with metastatic disease tend to have higher concentrations of circulating galectin-3 than those with only localized tumors (3). Our recent study has revealed that increased circulating galectin-3 is an important promoter of blood-borne metastasis in a mouse model (9). This effect of galectin-3 is shown to be partly attributed to galectin-3 interaction with the oncofetal Thomsen-Friedenreich (galactose␤1,3-N-acetyl-galactosamine ␣-, TF) disaccharide expressed on the cancer-associated transmembr...

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The Involvement of CD146 and Its Novel Ligand Galectin-1 in Apoptotic Regulation of Endothelial Cells

Cited by 62 publications

References 62 publications

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells

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