Journal
CELL REPORTS
Volume 31, Issue 11, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.107765
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Funding
- Marie Curie Individual Fellowship (H2020-MSCA-IF-2018) [841092]
- NIH/NIGMS [R25GM061347]
- FWO [GOC5320N]
- Marie Curie Actions (MSCA) [841092] Funding Source: Marie Curie Actions (MSCA)
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Tumor cell plasticity, including transdifferentiation, is thought to be a key driver of therapy failure, tumor dormancy, and metastatic dissemination. Although melanoma cells have been shown to adopt various phenotypic features in vitro, direct in vivo evidence of metastatic cell plasticity remains sparse. Here, we combine lineage tracing in a spontaneous metastatic mouse model of melanoma, advanced imaging, and single-cell RNA sequencing approaches to search for pathophysiologically relevant melanoma cellular states. We identify melanoma cells in intravascular niches of various metastatic organs. These cells are quiescent, are negative for characteristic melanoma markers, and acquire endothelial cell features. We replicate the endothelial transdifferentiation (EndT) finding in another mouse model and provide evidence of EndT in BRAF(V600E)-metastatic biopsies from human lung, brain, and small intestine, thus highlighting the clinical relevance of these findings. The tumor-vasculature pattern described herein may contribute to melanoma dormancy within metastatic organs and represent a putative target for therapies.
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