Synaptic proximity enables NMDAR signalling to promote brain metastasis.
Animals
Brain Neoplasms
/ physiopathology
Breast Neoplasms
/ pathology
Cell Line, Tumor
Female
Humans
Mice
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Neoplasm Metastasis
Receptors, N-Methyl-D-Aspartate
/ metabolism
Signal Transduction
/ physiology
Synapses
/ physiology
Synaptic Transmission
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
07
06
2018
accepted:
05
07
2019
pubmed:
20
9
2019
medline:
28
3
2020
entrez:
20
9
2019
Statut:
ppublish
Résumé
Metastasis-the disseminated growth of tumours in distant organs-underlies cancer mortality. Breast-to-brain metastasis (B2BM) is a common and disruptive form of cancer and is prevalent in the aggressive basal-like subtype, but is also found at varying frequencies in all cancer subtypes. Previous studies revealed parameters of breast cancer metastasis to the brain, but its preference for this site remains an enigma. Here we show that B2BM cells co-opt a neuronal signalling pathway that was recently implicated in invasive tumour growth, involving activation by glutamate ligands of N-methyl-D-aspartate receptors (NMDARs), which is key in model systems for metastatic colonization of the brain and is associated with poor prognosis. Whereas NMDAR activation is autocrine in some primary tumour types, human and mouse B2BM cells express receptors but secrete insufficient glutamate to induce signalling, which is instead achieved by the formation of pseudo-tripartite synapses between cancer cells and glutamatergic neurons, presenting a rationale for brain metastasis.
Identifiants
pubmed: 31534217
doi: 10.1038/s41586-019-1576-6
pii: 10.1038/s41586-019-1576-6
pmc: PMC6837873
mid: EMS83646
doi:
Substances chimiques
Receptors, N-Methyl-D-Aspartate
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
526-531Subventions
Organisme : European Research Council
Pays : International
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
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