Journal Article

DKFZ-2024-00267

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Lung endothelium exploits susceptible tumor cell states to instruct metastatic latency.

Jakab, M. V. (First author)DKFZ* ; Lee, K. H. (First author)DKFZ* ; Uvarovskii, A. ; Ovchinnikova, S. ; Kulkarni, S. R.DKFZ* ; Jakab, S. ; Rostalski, T.DKFZ* ; Spegg, C.DKFZ* ; Anders, S. ; Augustin, H. (Last author)DKFZ*

2024
Nature Research London

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Please use a persistent id in citations: doi:10.1038/s43018-023-00716-7

Abstract: In metastasis, cancer cells travel around the circulation to colonize distant sites. Due to the rarity of these events, the immediate fates of metastasizing tumor cells (mTCs) are poorly understood while the role of the endothelium as a dissemination interface remains elusive. Using a newly developed combinatorial mTC enrichment approach, we provide a transcriptional blueprint of the early colonization process. Following their arrest at the metastatic site, mTCs were found to either proliferate intravascularly or extravasate, thereby establishing metastatic latency. Endothelial-derived angiocrine Wnt factors drive this bifurcation, instructing mTCs to follow the extravasation-latency route. Surprisingly, mTC responsiveness towards niche-derived Wnt was established at the epigenetic level, which predetermined tumor cell behavior. Whereas hypomethylation enabled high Wnt activity leading to metastatic latency, methylated mTCs exhibited low activity and proliferated intravascularly. Collectively the data identify the predetermined methylation status of disseminated tumor cells as a key regulator of mTC behavior in the metastatic niche.

Note: DKFZ–ZMBH Alliance / 2024 May;5(5):716-730/ #EA:A190#LA:A190#

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Contributing Institute(s):

1. A190 Vaskuläre Onkologie und Metastasierung (A190)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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