Selectin ligands: will the real ones please stand up?

Varki, Ajit

doi:10.1172/jci119142

Cited by 287 publications

(244 citation statements)

References 75 publications

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“…L-selectin is a major carbohydrate-presenting ligand for E-selectin on human neutrophils identified in vitro but the actual in vivo ligand may be an unique mucin modified with N-linked sugars that has been characterized in murine cells and called E-selectin ligand-1 (Willmroth and Beaudet, 1999). L-selectin binds to at least three glycoproteins: Gly-CAM-1, CD-34, and MAdCAM-1 which are expressed on the endothelial cell surface, the most probable being a fucosylated variant of CD34 (Tedder et al, 1995;Varki, 1997). P-selectin interacts with its leukocyte counterpart, P-selectin glycoprotein ligand-1 (PSGL-1) which is, like CD34, modified with O-linked sialic acid and fucose (McEver and Cummings, 1997).…”

Section: Molecular Mechanisms That Control Leukocyte Extravasationmentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

621

429

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Endothelial cells play a wide variety of critical roles in the control of vascular function. Indeed, since the early 1980s, the accumulating knowledge of the endothelial cell structure as well as of the functional properties of the endothelial cells shifted their role from a passive membrane or barrier to a complex tissue with complex functions adaptable to needs specific in time and location. Hence, it participates to all aspects of the vascular homeostasis but also to physiological or pathological processes like thrombosis, inflammation, or vascular wall remodeling. Some of the most important endothelial functions will be described in the following review and more specifically, their role in blood vessel formation, in coagulation and fibribolysis, in the regulation of vascular tone as well as their participation in inflammatory reactions and in tumor neoangiogenesis. J. Cell. Physiol. 196: 430–443, 2003. © 2003 Wiley‐Liss, Inc.

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Section: Molecular Mechanisms That Control Leukocyte Extravasationmentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

621

429

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“…Fractionation of in vivo [3 H]-glucosamine labeled PSGL-1 glycopeptides on Concanavalin A-Sepharose (0.8 ml bed volume) was done essentially as described by Merkle and Cummings [22]. Bound glycopeptides were sequentially eluted with 10 mM amethylglucoside followed by 100 m M a-methylmannoside at 55 o C; fraction volume was 2 ml.…”

Section: Lectin Chromatographymentioning

confidence: 99%

“…The interaction(s) between the selectins and the target cells is mediated by oligosaccharide structures conjugated to specific ligand molecules expressed on the target cell surfaces. These ligand molecules may be recognized by one, two or all three of the selectins [1][2][3]. Although available data suggest that the interaction(s) between the selectins and their ligands in most cases is mediated by O-linked oligosaccharide structures, spe-cific binding of E-selectin to N-linked oligosaccharides has been reported [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Partial characterization of the N-linked oligosaccharide structures on P-selectin glycoprotein ligand-1 (PSGL-1)

Aeed¹,

Geng

Asa³

et al. 2001

Cell Res

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PSGL-1, a specific ligand for P-, E-and L-selectin, was isolated from in vivo [ 3 H]-glucosamine labeled HL-60 cells by a combination of wheat germ agglutinin-agarose and P-or E-selectin-agarose chromatography. N-linked oligosaccharides were released from the purified, denatured ligand molecule by peptide: N-glycosidase F treatment and, following separation by Sephacryl S-200 chromatography, partially characterized using lectin, ion-exchange and size-exclusion chromatography in combination with glycosidase digestions. The data obtained suggest that the N-glycans on PSGL-1 are predominantly core-fucosylated, multiantennary complex type structures with extended, poly-N-acetyllactosamine containing outer chains. A portion of the outer chains appears to be substituted with fucose indicating that the N-glycans, in addition to the Oglycans on PSGL-1, may be involved in selectin binding.

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“…11,12 Functionally, the binding of selectins to leukocytes requires sialylated and fucosylated carbohydrate structures; their prototypes are SAa2-3Galb1-4(Fuca1-3)GlcNAc and SAa2-3Galb1-3(Fuca1-4)GlcNAc, referred to as sLe x and sLe a , respectively. [13][14][15] Both sLe x and sLe a are involved in selectin-mediated adhesion of cancer cells to vascular endothelium, and these determinants are thought to be closely associated with hematogenous metastasis of cancers. [16][17][18][19] These determinants not only are markers for cancer but also are functionally implicated in the malignant behavior of cancer cells.…”

mentioning

confidence: 99%

Deficiency in surface expression of E‐selectin ligand promotes lung colonization in a mouse model of breast cancer

Monzavi‐Karbassi

Whitehead

Jousheghany

et al. 2005

Intl Journal of Cancer

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Expression of sialyl Lewis x (sLe x ) and sLe a on tumor cells is thought to facilitate metastasis by promoting cell adhesion to selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing tumor cells that are injected directly into the blood. We investigated the relative role of sLe x oligosaccharide in the dissemination of breast carcinoma, employing a spontaneous murine metastasis model. An sLe x deficient subpopulation of the 4T1 mammary carcinoma cell line was produced by negative selection using the sLe x -reactive KM93 MAb. This subpopulation was negative for E-selectin binding but retained P-selectin binding. Both sLe x -negative and -positive cells grew at the same rate; however, sLe x -negative cells spread more efficiently on plates and had greater motility in wound-scratch assays. Mice inoculated in the mammary fat pad with sLe x -negative and -positive variants produced lung metastases. However, the number of lung metastases was significantly increased in the group inoculated with the sLe x -negative variant (p 5 0.0031), indicating that negative selection for the sLe x epitope resulted in enrichment for a subpopulation of cells with a high metastatic phenotype. Cell variants demonstrated significant differences in cellular morphology and pattern of tumor growth in primary and secondary tumor sites. These results strongly suggest that loss of sLe x may facilitate the metastatic process by contributing to escape from the primary tumor mass. ' 2005 Wiley-Liss, Inc.Key words: sialyl Lewis x antigen; metastasis; 4T1 cells; breast cancer Tumor metastasis is a multistep process requiring detachment of malignant cells from the primary tumor, penetration of blood or lymph vessels, attachment to endothelium of distant organs and formation of new tumor foci. 1,2 Tissue invasion and metastasis of tumor cells are highly dependent on cell-cell interactions, many of which involve alterations in cell surface glycosylation patterns. 3,4 Although adhesion pathways utilized by tumor cells show considerable diversity, members of the selectin family of molecules and numerous neolactoseries antigens highly expressed on the tumor cell surface are involved in tumor metastasis by mediating binding of blood-borne tumor cells via E-and/or P-selectin to vascular endothelium. [5][6][7][8][9][10] Much of what we know about selectin interactions comes from studies of leukocytes. 11,12 Functionally, the binding of selectins to leukocytes requires sialylated and fucosylated carbohydrate structures; their prototypes are SAa2-3Galb1-4(Fuca1-3)GlcNAc and SAa2-3Galb1-3(Fuca1-4)GlcNAc, referred to as sLe x and sLe a , respectively. [13][14][15] Both sLe x and sLe a are involved in selectin-mediated adhesion of cancer cells to vascular endothelium, and these determinants are thought to be closely associated with hematogenous metastasis of cancers. [16][17][18][19] These determinants not only are markers for cancer but also are functionally implicated ...

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Selectin ligands: will the real ones please stand up?

Cited by 287 publications

References 75 publications

Endothelial cell functions

Endothelial cell functions

Partial characterization of the N-linked oligosaccharide structures on P-selectin glycoprotein ligand-1 (PSGL-1)

Deficiency in surface expression of E‐selectin ligand promotes lung colonization in a mouse model of breast cancer

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