Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
10
04
2018
accepted:
22
05
2019
entrez:
3
7
2019
pubmed:
3
7
2019
medline:
27
11
2019
Statut:
ppublish
Résumé
Most human tumours are heterogeneous, composed of cellular clones with different properties present at variable frequencies. Highly heterogeneous tumours have poor clinical outcomes, yet the underlying mechanism remains poorly understood. Here, we show that minor subclones of breast cancer cells expressing IL11 and FIGF (VEGFD) cooperate to promote metastatic progression and generate polyclonal metastases composed of driver and neutral subclones. Expression profiling of the epithelial and stromal compartments of monoclonal and polyclonal primary and metastatic lesions revealed that this cooperation is indirect, mediated through the local and systemic microenvironments. We identified neutrophils as a leukocyte population stimulated by the IL11-expressing minor subclone and showed that the depletion of neutrophils prevents metastatic outgrowth. Single-cell RNA-seq of CD45
Identifiants
pubmed: 31263265
doi: 10.1038/s41556-019-0346-x
pii: 10.1038/s41556-019-0346-x
pmc: PMC6609451
mid: EMS83263
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
879-888Subventions
Organisme : Swiss National Science Foundation
ID : 175139
Pays : Switzerland
Organisme : NCI NIH HHS
ID : T32 CA207021
Pays : United States
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