이기홍 (Heidelberg University, DKFZ-ZMBH Alliance) | 한빛사논문 > 한빛사

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조회395

이기홍Ki Hong Lee

Heidelberg University, DKFZ-ZMBH Alliance

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Nat. Cancer, Feb 02 2024, | https://doi.org/10.1038/s43018-023-00716-7 Lung endothelium exploits susceptible tumor cell states to instruct metastatic latency

Moritz Jakab ^1,2,3,7,*, Ki Hong Lee^1,2,3,7, Alexey Uvarovskii ^4,5, Svetlana Ovchinnikova ^4,6, Shubhada R. Kulkarni ^1,2, Sevinç Jakab ³, Till Rostalski ^1,2, Carleen Spegg ², Simon Anders ^4,6 & Hellmut G. Augustin ^1,2,*

¹European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
²Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg (DKFZ–ZMBH Alliance), Heidelberg, Germany.
³Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
⁴Center for Molecular Biology, Heidelberg University, Heidelberg, Germany.
⁵Evotec SE, Göttingen, Germany.
⁶Bioquant Center, Heidelberg University, Heidelberg, Germany.
⁷These authors contributed equally: Moritz Jakab, Ki Hong Lee.

^*Corresponding authors: correspondence to Moritz Jakab or Hellmut G. Augustin

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.

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형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-07)
연구진국외 연구진
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