β1-6 Branching of Asn-Linked Oligosaccharides Is Directly Associated with Metastasis

Dennis, James W.; Laferté, Suzanne; Waghorne, Carol; Breitman, Martin L.; Kerbel, Robert S.

doi:10.1126/science.2953071

Cited by 885 publications

(530 citation statements)

References 26 publications

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“…Increased cell surface N-linked b1fi6(GlcNAcb1fi6Man is associated with increased metastatic properties. [38][39][40] L-PHA recognizes b(1fi6) branching structures with high affinity and specificity. This lectin bound to all cell variants with no significant difference.…”

Section: Sle X Is the Major Carbohydrate Determinant That Differs Betmentioning

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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Section: Sle X Is the Major Carbohydrate Determinant That Differs Betmentioning

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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“…It has been reported that an aberrant glycosylation induced by MGAT5 is associated with tumor malignant transformation, including tumor invasion and metastasis. Enhanced activity of MGAT5, resulting in an increase of β1-6-branched oligosaccharides on the cell-surface, may contribute to the increased invasive potential of tumor cells [19]. Upregulated MGAT5 activity has been reported in human breast cancer, hepatocarcinoma and colon cancer [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

N-acetylglucosaminyltransferase V inhibits the invasion of trophoblast cells by attenuating MMP2/9 activity in early human pregnancy

et al. 2015

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“…On the other hand, an increasing body of evidence suggests that N-glycosylation is also important for the cell adhesion. Changes in the N-glycan structures of those adhesive molecules can affect cell-cell and cell-ECM interactions, thereby affecting cell adhesion, migration and tumor invasion [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Potential roles of N-glycosylation in cell adhesion

Isaji

et al. 2012

Glycoconj J

127

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The functional units of cell adhesion are typically multiprotein complexes made up of three general classes of proteins; the adhesion receptors, the cell-extracellular matrix (ECM) proteins, and the cytoplasmic plaque/peripheral membrane proteins. The cell adhesion receptors are usually transmembrane glycoproteins (for example E-cadherin and integrin) that mediate binding at the extracellular surface and determine the specificity of cell-cell and cell-ECM recognition. E-cadherin-mediated cell-cell adhesion can be both temporally and spatially regulated during development, and represents a key step in the acquisition of the invasive phenotype for many tumors. On the other hand, integrin-mediated cell-ECM interactions play important roles in cytoskeleton organization and in the transduction of intracellular signals to regulate various processes such as proliferation, differentiation and cell migration. ECM proteins are typically large glycoproteins, including the collagens, fibronectins, laminins, and proteoglycans that assemble into fibrils or other complex macromolecular arrays. The most of these adhesive proteins are glycosylated. Here, we focus mainly on the modification of N-glycans of integrins and laminin-332, and a mutual regulation between cell adhesion and bisected N-glycan expression, to address the important roles of N-glycans in cell adhesion.

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β1-6 Branching of Asn-Linked Oligosaccharides Is Directly Associated with Metastasis

Cited by 885 publications

References 26 publications

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

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

N-acetylglucosaminyltransferase V inhibits the invasion of trophoblast cells by attenuating MMP2/9 activity in early human pregnancy

Potential roles of N-glycosylation in cell adhesion

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