Systematic analysis of the human tumor cell binding to human vs. murine E- and P-selectin under static vs. dynamic conditions.
adhesion
carbohydrate-binding protein
metastasis
shear stress
tumor cell biology
Journal
Glycobiology
ISSN: 1460-2423
Titre abrégé: Glycobiology
Pays: England
ID NLM: 9104124
Informations de publication
Date de publication:
20 08 2020
20 08 2020
Historique:
received:
30
01
2020
revised:
22
02
2020
accepted:
26
02
2020
pubmed:
28
2
2020
medline:
21
10
2021
entrez:
28
2
2020
Statut:
ppublish
Résumé
Endothelial E- and P-selectins promote metastasis formation by interacting with sialyl-Lewis X and A (sLeX/sLeA) on circulating tumor cells. This interaction precedes extravasation and can take place under dynamic and static conditions. Metastasis formation is often studied in xenograft models. However, it is unclear whether species differences exist in the ligand specificity of human (h) vs. murine (m) selectins and whether different ligands are functional under dynamic vs. static conditions. We systematically compared the h vs. m E- and P-selectin (ESel/PSel) binding of a range of human tumor cells under dynamic vs. static conditions. The tumor cells were categorized by their sLeA/X status (sLeA+/sLeX+, sLeA-/sLeX+ and sLeA-/sLeX-). The general biological nature of the tumor-selectin interaction was analyzed by applying several tumor cell treatments (anti-sLeA/X blockade, neuraminidase, pronase and inhibition of O/N-glycosylation). We observed remarkable differences in the static vs. dynamic interaction of tumor cells with h vs. m ESel/PSel depending on their sLeA/X status. The tumor cell treatments mostly affected either static or dynamic as well as either h- or m-selectin interaction. mESel showed a higher diversity of potential ligands than hESel. Inhibition of O-GalNAc-glycosylation also affected glycosphingolipid synthesis. Summarized, different ligands on human tumor cells are functional under static vs. dynamic conditions and for the interaction with human vs. murine ESel/PSel. Non-canonical selectin ligands lacking the sLeA/X glycan epitopes exist on human tumor cells. These findings have important implications for the current development of glycomimetic, antimetastatic drugs and encourage the development of immunodeficient mice with humanized selectins.
Identifiants
pubmed: 32103235
pii: 5760696
doi: 10.1093/glycob/cwaa019
pmc: PMC7443332
doi:
Substances chimiques
E-Selectin
0
P-Selectin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
695-709Informations de copyright
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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