Targeting colony stimulating factor-1 receptor signalling to treat ectopic pregnancy.
Cell Death
/ drug effects
Cell Line
Cell Movement
/ drug effects
Female
Gene Expression Regulation
/ drug effects
Humans
Macrophage Colony-Stimulating Factor
/ metabolism
Molecular Targeted Therapy
Pregnancy
Pregnancy, Ectopic
/ drug therapy
Receptor, Macrophage Colony-Stimulating Factor
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Trophoblasts
/ drug effects
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 09 2020
24 09 2020
Historique:
received:
15
04
2020
accepted:
07
09
2020
entrez:
25
9
2020
pubmed:
26
9
2020
medline:
22
12
2020
Statut:
epublish
Résumé
1-2% of pregnancies are ectopic, the majority implanting in the Fallopian tube. A single, systemic dose of methotrexate, a DNA-synthesis (S phase) inhibitor, has been used since 1991 for outpatient treatment of women with stable EP. However, methotrexate has limited clinical and cost effectiveness, restricting its use to 25-30% of these women. There is an unmet need for better medical treatment for EP. Colony stimulating factor-1 (CSF-1) promotes placentation and creates a pro-inflammatory environment that is fundamental for the maintenance of a normal pregnancy. We hypothesised that CSF-1 is also involved in the placentation and maintenance of an EP. Herein, we demonstrate the immunolocalisation of the CSF-1 receptor (CSF-1R) as well as its ligand (CSF-1) in immortalised first trimester trophoblast cells. We show that a specific CSF-1R kinase inhibitor, GW2580, abolishes CSF-1 induced trophoblast cell proliferation and migration and can be cytotoxic. We then demonstrate the expression of CSF-1R and CSF-1 in the cytotrophoblast and syncytiotrophoblast within ectopic implantation sites from women with EP. Our data suggests that CSF-1 is involved in the survival and proliferation of trophoblast cells in EP. This suggests that pharmacological disruption of CSF-1/CSF-1R signaling axis could be the basis of a new therapeutic for EP.
Identifiants
pubmed: 32973322
doi: 10.1038/s41598-020-72785-y
pii: 10.1038/s41598-020-72785-y
pmc: PMC7519033
doi:
Substances chimiques
Macrophage Colony-Stimulating Factor
81627-83-0
Receptor, Macrophage Colony-Stimulating Factor
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15638Subventions
Organisme : Chief Scientist Office
ID : CZB/4/513
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1100356
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108766/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0802808
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N022556/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N024524/1
Pays : United Kingdom
Organisme : Department of Health
ID : 14/150/03
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
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