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. 2019 Sep 26;55(5):1033–1048. doi: 10.3892/ijo.2019.4886

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Copyright: © Ferreira et al.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Schematic representation of the multistep metastatic process in cancer and main structures involved. (A) Contribution of sLe^x/sLe^a antigens in facilitating cell adhesion to E-selectins. There are four main steps in the extravasation process, including tethering and rolling, integrin activation, firm adhesion and transendothelial migration. Metastatic dissemination is facilitated by interactions between tumour cells and endothelium in distant tissues. These interactions are mediated by E-selectins expressed by activated endothelial cells and the corresponding E-selectin ligands expressed on the cell surface of cancer cells. These ligands are prototypically the sLe^x and sLe^a antigens, displayed on cell surface proteins or lipid scaffolds. (B) Structure and schematic representation of the biosynthesis of sialyl Lewis antigens. sLe^a and sLe^x antigens are sialofucosylated isomer tetrasaccharides, derived from type 1 or type 2 sugar chains, respectively, attached to N- or O-glycan residues. The two types of structures are sialylated by the action of the indicated α2,3-sialyltransferases and successively fucosylated by the action of the FUT3 (in type 1 chains), and FUT3, 4, 5, 6 or 7 (in type 2 chains). FUT, fucosyltransferase; sLe^a/x, sialyl Lewis a/x.

Schematic representation of the multistep metastatic process in cancer and main structures involved. (A) Contribution of sLe^x/sLe^a antigens in facilitating cell adhesion to E-selectins. There are four main steps in the extravasation process, including tethering and rolling, integrin activation, firm adhesion and transendothelial migration. Metastatic dissemination is facilitated by interactions between tumour cells and endothelium in distant tissues. These interactions are mediated by E-selectins expressed by activated endothelial cells and the corresponding E-selectin ligands expressed on the cell surface of cancer cells. These ligands are prototypically the sLe^x and sLe^a antigens, displayed on cell surface proteins or lipid scaffolds. (B) Structure and schematic representation of the biosynthesis of sialyl Lewis antigens. sLe^a and sLe^x antigens are sialofucosylated isomer tetrasaccharides, derived from type 1 or type 2 sugar chains, respectively, attached to N- or O-glycan residues. The two types of structures are sialylated by the action of the indicated α2,3-sialyltransferases and successively fucosylated by the action of the FUT3 (in type 1 chains), and FUT3, 4, 5, 6 or 7 (in type 2 chains). FUT, fucosyltransferase; sLe^a/x, sialyl Lewis a/x.