Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Lauc, Gordan; Heffer-Lauc, Marija

doi:10.1016/j.bbagen.2005.11.014

Cited by 74 publications

(51 citation statements)

References 277 publications

(300 reference statements)

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“…Numerous factors can influence the incorporation and the rate of transfer of exogenously added gangliosides into cell membranes. Under some conditions, gangliosides added at lower concentrations could be more effective at entering membranes than when added at higher concentrations, as a result of micelle formation at higher concentrations (44). Collectively, these findings indicate that the influence of gangliosides on angiogenesis and cell signaling events is dependent to a large extent on the type of microenvironment and on the concentrations of gangliosides and growth factors in the microenvironment.…”

Section: Discussionmentioning

confidence: 66%

Thematic Review Series: Sphingolipids. Ganglioside GM3 suppresses the proangiogenic effects of vascular endothelial growth factor and ganglioside GD1a

Mukherjee

Faber

Shelton

et al. 2008

Journal of Lipid Research

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Gangliosides are sialic acid-containing glycosphingolipids that have long been associated with tumor malignancy and metastasis. Mounting evidence suggests that gangliosides also modulate tumor angiogenesis. Tumor cells shed gangliosides into the microenvironment, which produces both autocrine and paracrine effects on tumor cells and tumor-associated host cells. In this study, we show that the simple monosialoganglioside GM3 counteracts the proangiogenic effects of vascular endothelial growth factor (VEGF) and of the complex disialoganglioside GD1a. GM3 suppressed the action of VEGF and GD1a on the proliferation of human umbilical vein endothelial cells (HUVECs) and inhibited the migration of HUVECs toward VEGF as a chemoattractant. Enrichment of added GM3 in the HUVEC membrane also reduced the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2) and downstream Akt. Moreover, GM3 reduced the proangiogenic effects of GD1a and growth factors in the in vivo Matrigel plug assay. Inhibition of GM3 biosynthesis with the glucosyl transferase inhibitor, N-butyldeoxynojirimycin (N B-DNJ), increased HUVEC proliferation and the phosphorylation of VEGFR-2 and Akt. The effects of N B-DNJ on HUVECs were reversed with the addition of GM3.

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Section: Discussionmentioning

confidence: 66%

Thematic Review Series: Sphingolipids. Ganglioside GM3 suppresses the proangiogenic effects of vascular endothelial growth factor and ganglioside GD1a

Mukherjee

Faber

Shelton

et al. 2008

Journal of Lipid Research

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“…5Be and Refs. 30, 32), including type I cells, could result from gene expression and/or shedding and membrane insertion of CEACAM6, a known property of GPI proteins (27) and of CEACAM6 in A549 cells (31). We, therefore, further examined this issue as summarized in Fig.…”

Section: Resultsmentioning

confidence: 99%

Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung

Chapin

Bailey

Gonzales

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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PL. Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung. Am J Physiol Lung Cell Mol Physiol 302: L216 -L225, 2012. First published October 28, 2011 doi:10.1152/ajplung.00055.2011.-Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycophosphatidylinositol-anchored protein expressed in epithelial cells of various primate tissues. It binds gram-negative bacteria and is overexpressed in human cancers. CEACAM6 is associated with lamellar bodies of cultured type II cells of human fetal lung and protects surfactant function in vitro. In this study, we characterized CEACAM6 expression in vivo in human lung. CEACAM6 was present in lung lavage of premature infants at birth and increased progressively in intubated infants with lung disease. Of surfactant-associated CEACAM6, ϳ80% was the fully glycosylated, 90-kDa form that contains the glycophosphatidylinositol anchor, and the concentration (3.9% of phospholipid for adult lung) was comparable to that for surfactant proteins (SP)-A/B/C. We examined the affinity of CEACAM6 by purification of surfactant on density gradient centrifugation; concentrations of CEACAM6 and SP-B per phospholipid were unchanged, whereas levels of total protein and SP-A decreased by 60%. CEACAM6 mRNA content decreased progressively from upper trachea to peripheral fetal lung, whereas protein levels were similar in all regions of adult lung, suggesting proximal-to-distal developmental expression in lung epithelium. In adult lung, most type I cells and ϳ50% of type II cells were immunopositive. We conclude that CEACAM6 is expressed by alveolar and airway epithelial cells of human lung and is secreted into lung-lining fluid, where fully glycosylated protein binds to surfactant. Production appears to be upregulated during neonatal lung disease, perhaps related to roles of CEACAM6 in surfactant function, cell proliferation, and innate immune defense. alveolar type II cells; lung lining fluid; surfactant; airway epithelium CARCINOEMBRYONIC CELL ADHESION molecule 6 (CEACAM6) (also called NCA, NCA-50/90, and CD66c) is a member of the carcinoembryonic antigen (CEA) gene family, consisting of 29 related genes. CEA proteins function as intercellular homophilic and heterophilic adhesion molecules and have signaling properties (18). CEACAM6 contains a glycophosphatidylinositol (GPI) membrane anchor (23) and is targeted to lipid rafts in apical membranes of polarized epithelial cells (26). CEACAM6 binds a variety of gram-negative bacteria and mediates internalization and phagocytosis, participating in innate immune defense in the intestine (13). The CEACAM6 gene is not present in rodents, and its emergence in primates may represent pathogen-host coevolution, providing different protein structures with selective bacterial binding properties.Expression of CEACAM6 and closely related CEACAM5 is deregulated and overexpressed in cancers of colorectal epithelium, with surface levels inversely correlated with both the degree of colonocyte differentiat...

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“…Given that serum/plasma GSLs originate from a variety of tissues and enter the circulation as a result of shedding processes ( 13 ), the serum/plasma GSL-glycome would be a good tool with which to identify and/or screen diseaserelated biomarkers. The presence of gangliosides in human serum was fi rst described in 1963 ( 14 ).…”

Section: Acid Hydrolysis and Sequential Exoglycosidase Digestionmentioning

confidence: 99%

Quantitative GSL-glycome analysis of human whole serum based on an EGCase digestion and glycoblotting method

Furukawa

Sakaï

Yokota

et al. 2015

Journal of Lipid Research

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Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Cited by 74 publications

References 277 publications

Thematic Review Series: Sphingolipids. Ganglioside GM3 suppresses the proangiogenic effects of vascular endothelial growth factor and ganglioside GD1a

Thematic Review Series: Sphingolipids. Ganglioside GM3 suppresses the proangiogenic effects of vascular endothelial growth factor and ganglioside GD1a

Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung

Quantitative GSL-glycome analysis of human whole serum based on an EGCase digestion and glycoblotting method

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