Author
Listed:
- Panagiotis Karras
(VIB
KU Leuven)
- Ignacio Bordeu
(University of Cambridge
The Wellcome Trust/CRUK Gurdon Institute, University of Cambridge
Universidad de Chile)
- Joanna Pozniak
(VIB
KU Leuven)
- Ada Nowosad
(VIB
KU Leuven)
- Cecilia Pazzi
(VIB
KU Leuven)
- Nina Raemdonck
(VIB
KU Leuven)
- Ewout Landeloos
(VIB
KU Leuven)
- Yannick Herck
(UZ Leuven)
- Dennis Pedri
(VIB
KU Leuven)
- Greet Bervoets
(VIB
KU Leuven)
- Samira Makhzami
(VIB
KU Leuven)
- Jia Hui Khoo
(BGI-Shenzhen)
- Benjamin Pavie
(VIB Center for Brain and Disease Research
VIB Center for Inflammation Research
Ghent University)
- Jochen Lamote
(VIB)
- Oskar Marin-Bejar
(VIB
KU Leuven)
- Michael Dewaele
(VIB
KU Leuven)
- Han Liang
(BGI-Shenzhen)
- Xingju Zhang
(BGI-Shenzhen)
- Yichao Hua
(KU Leuven
VIB)
- Jasper Wouters
(VIB-KU Leuven
KU Leuven)
- Robin Browaeys
(VIB Center for Inflammation Research
Ghent University)
- Gabriele Bergers
(KU Leuven
VIB)
- Yvan Saeys
(VIB Center for Inflammation Research
Ghent University)
- Francesca Bosisio
(KU Leuven)
- Joost Oord
(KU Leuven)
- Diether Lambrechts
(VIB
KU Leuven)
- Anil K. Rustgi
(Columbia University Irving Medical Center)
- Oliver Bechter
(UZ Leuven)
- Cedric Blanpain
(Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB))
- Benjamin D. Simons
(University of Cambridge
The Wellcome Trust/CRUK Gurdon Institute, University of Cambridge
University of Cambridge)
- Florian Rambow
(VIB
KU Leuven
Institute for AI in Medicine (IKIM), University Hospital Essen
University Duisburg-Essen)
- Jean-Christophe Marine
(VIB
KU Leuven)
Abstract
Although melanoma is notorious for its high degree of heterogeneity and plasticity1,2, the origin and magnitude of cell-state diversity remains poorly understood. Equally, it is unclear whether growth and metastatic dissemination are supported by overlapping or distinct melanoma subpopulations. Here, by combining mouse genetics, single-cell and spatial transcriptomics, lineage tracing and quantitative modelling, we provide evidence of a hierarchical model of tumour growth that mirrors the cellular and molecular logic underlying the cell-fate specification and differentiation of the embryonic neural crest. We show that tumorigenic competence is associated with a spatially localized perivascular niche, a phenotype acquired through an intercellular communication pathway established by endothelial cells. Consistent with a model in which only a fraction of cells are fated to fuel growth, temporal single-cell tracing of a population of melanoma cells with a mesenchymal-like state revealed that these cells do not contribute to primary tumour growth but, instead, constitute a pool of metastatic initiating cells that switch cell identity while disseminating to secondary organs. Our data provide a spatially and temporally resolved map of the diversity and trajectories of melanoma cell states and suggest that the ability to support growth and metastasis are limited to distinct pools of cells. The observation that these phenotypic competencies can be dynamically acquired after exposure to specific niche signals warrant the development of therapeutic strategies that interfere with the cancer cell reprogramming activity of such microenvironmental cues.
Suggested Citation
Panagiotis Karras & Ignacio Bordeu & Joanna Pozniak & Ada Nowosad & Cecilia Pazzi & Nina Raemdonck & Ewout Landeloos & Yannick Herck & Dennis Pedri & Greet Bervoets & Samira Makhzami & Jia Hui Khoo & , 2022.
"A cellular hierarchy in melanoma uncouples growth and metastasis,"
Nature, Nature, vol. 610(7930), pages 190-198, October.
Handle:
RePEc:nat:nature:v:610:y:2022:i:7930:d:10.1038_s41586-022-05242-7
DOI: 10.1038/s41586-022-05242-7
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Citations
Citations are extracted by the
CitEc Project, subscribe to its
RSS feed for this item.
Cited by:
- Guillaume Harmange & Raúl A. Reyes Hueros & Dylan L. Schaff & Benjamin Emert & Michael Saint-Antoine & Laura C. Kim & Zijian Niu & Shivani Nellore & Mitchell E. Fane & Gretchen M. Alicea & Ashani T. W, 2023.
"Disrupting cellular memory to overcome drug resistance,"
Nature Communications, Nature, vol. 14(1), pages 1-17, December.
- Michael F. Emmons & Richard L. Bennett & Alberto Riva & Kanchan Gupta & Larissa Anastasio Da Costa Carvalho & Chao Zhang & Robert Macaulay & Daphne Dupéré-Richér & Bin Fang & Edward Seto & John M. Koo, 2023.
"HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis,"
Nature Communications, Nature, vol. 14(1), pages 1-18, December.
- F. Nadalin & M. J. Marzi & M. Pirra Piscazzi & P. Fuentes-Bravo & S. Procaccia & M. Climent & P. Bonetti & C. Rubolino & B. Giuliani & I. Papatheodorou & J. C. Marioni & F. Nicassio, 2024.
"Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution,"
Nature Communications, Nature, vol. 15(1), pages 1-23, December.
- Martin Lauss & Bengt Phung & Troels Holz Borch & Katja Harbst & Kamila Kaminska & Anna Ebbesson & Ingrid Hedenfalk & Joan Yuan & Kari Nielsen & Christian Ingvar & Ana Carneiro & Karolin Isaksson & Kri, 2024.
"Molecular patterns of resistance to immune checkpoint blockade in melanoma,"
Nature Communications, Nature, vol. 15(1), pages 1-14, December.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:610:y:2022:i:7930:d:10.1038_s41586-022-05242-7. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.