Exploiting the Receptor-Binding Domains of R-Spondin 1 to Target Leucine-Rich Repeat-Containin G-Coupled Protein Receptor 5-Expressing Stem Cells in Ovarian Cancer.
Journal
The Journal of pharmacology and experimental therapeutics
ISSN: 1521-0103
Titre abrégé: J Pharmacol Exp Ther
Pays: United States
ID NLM: 0376362
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
02
11
2022
accepted:
08
02
2023
pmc-release:
01
05
2024
medline:
12
4
2023
pubmed:
28
2
2023
entrez:
27
2
2023
Statut:
ppublish
Résumé
Leucine-rich repeat-containing G-protein-coupled receptor (LGR5) and LGR6 mark epithelial stem cells in normal tissues and tumors. They are expressed by stem cells in the ovarian surface and fallopian tube epithelia from which ovarian cancer arises. High-grade serous ovarian cancer is unique in expressing unusually high levels of LGR5 and LGR6 mRNA. R-spondins are the natural ligands for LGR5 and LGR6 to which they bind with nanomolar affinity. To target stem cells in ovarian cancer, we used the sortase reaction to site-specifically conjugate the potent cytotoxin monomethyl auristatin E (MMAE) via a protease sensitive linker to the two furin-like domains of RSPO1 (Fu
Identifiants
pubmed: 36849411
pii: jpet.122.001495
doi: 10.1124/jpet.122.001495
pmc: PMC10108443
doi:
Substances chimiques
Leucine
GMW67QNF9C
Peptide Hydrolases
EC 3.4.-
Receptors, G-Protein-Coupled
0
Thrombospondins
0
LGR5 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
95-105Informations de copyright
Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.
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