Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation

Nathaniel R. Campbell; Anjali Rao; Miranda V. Hunter; Magdalena K. Sznurkowska; Luzia Briker; Maomao Zhang; Maayan Baron; Silja Heilmann; Maxime Deforet; Colin Kenny; Lorenza P. Ferretti; Ting-Hsiang Huang; Sarah Perlee; Manik Garg; Jérémie Nsengimana; Massimo Saini; Emily Montal; Mohita Tagore; Julia Newton-Bishop; Mark R. Middleton; Pippa Corrie; David J. Adams; Roy Rabbie; Nicola Aceto; Mitchell P. Levesque; Robert A. Cornell; Itai Yanai; Joao B. Xavier; Richard M. White

doi:10.1016/j.devcel.2021.08.018

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Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation

Journal article

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Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation

Nathaniel R. Campbell, Anjali Rao, Miranda V. Hunter, Magdalena K. Sznurkowska, Luzia Briker, Maomao Zhang, Maayan Baron, Silja Heilmann, Maxime Deforet, Colin Kenny, …

Developmental cell, Vol.56(20), pp.2808-2825.e10

10/25/2021

DOI: 10.1016/j.devcel.2021.08.018

PMCID: PMC8551056

PMID: 34529939

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Abstract

Melanomas can have multiple coexisting cell states, including proliferative (PRO) versus invasive (INV) subpopulations that represent a “go or grow” trade-off; however, how these populations interact is poorly understood. Using a combination of zebrafish modeling and analysis of patient samples, we show that INV and PRO cells form spatially structured heterotypic clusters and cooperate in the seeding of metastasis, maintaining cell state heterogeneity. INV cells adhere tightly to each other and form clusters with a rim of PRO cells. Intravital imaging demonstrated cooperation in which INV cells facilitate dissemination of less metastatic PRO cells. We identified the TFAP2 neural crest transcription factor as a master regulator of clustering and PRO/INV states. Isolation of clusters from patients with metastatic melanoma revealed a subset with heterotypic PRO-INV clusters. Our data suggest a framework for the co-existence of these two divergent cell populations, in which heterotypic clusters promote metastasis via cell-cell cooperation. [Display omitted] •Cluster formation is a pro-metastatic phenotype associated with the INV state•PRO and INV cooperate in metastasis via heterotypic circulating tumor cell clusters•TFAP2 modulates PRO versus INV state, clustering, and metastasis Proliferative (PRO) and invasive (INV) cell states coexist in melanoma. Campbell et al. demonstrate that PRO and INV cells cooperate in metastasis via heterotypic circulating tumor cell (CTC) clusters and identify TFAP2 as a key mediator. Their work highlights a role for collective dissemination in melanoma metastasis.

circulating tumor cell cluster

cluster

cooperation

melanoma

metastasis

TFAP2

zebrafish

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Title: Subtitle: Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation
Creators: Nathaniel R. Campbell - Memorial Sloan Kettering Cancer Center
Anjali Rao - Institute for Computational Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Miranda V. Hunter - Memorial Sloan Kettering Cancer Center
Magdalena K. Sznurkowska - Department of Biology, Institute of Molecular Health Sciences; Swiss Federal Institute of Technology (ETH) Zurich; 8093 Zurich Switzerland
Luzia Briker - University Hospital of Zurich
Maomao Zhang - Memorial Sloan Kettering Cancer Center
Maayan Baron - Institute for Computational Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Silja Heilmann - Memorial Sloan Kettering Cancer Center
Maxime Deforet - Memorial Sloan Kettering Cancer Center
Colin Kenny - University of Iowa
Lorenza P. Ferretti - University of Zurich
Ting-Hsiang Huang - Memorial Sloan Kettering Cancer Center
Sarah Perlee - Memorial Sloan Kettering Cancer Center
Manik Garg - European Bioinformatics Institute
Jérémie Nsengimana - University of Leeds
Massimo Saini - Department of Biology, Institute of Molecular Health Sciences; Swiss Federal Institute of Technology (ETH) Zurich; 8093 Zurich Switzerland
Emily Montal - Memorial Sloan Kettering Cancer Center
Mohita Tagore - Memorial Sloan Kettering Cancer Center
Julia Newton-Bishop - University of Leeds
Mark R. Middleton - University of Oxford
Pippa Corrie - Cambridge University Hospitals NHS Foundation Trust
David J. Adams - Wellcome Sanger Institute
Roy Rabbie - Cambridge University Hospitals NHS Foundation Trust
Nicola Aceto - Department of Biology, Institute of Molecular Health Sciences; Swiss Federal Institute of Technology (ETH) Zurich; 8093 Zurich Switzerland
Mitchell P. Levesque - University Hospital of Zurich
Robert A. Cornell - University of Iowa
Itai Yanai - Institute for Computational Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Joao B. Xavier - Memorial Sloan Kettering Cancer Center
Richard M. White - Memorial Sloan Kettering Cancer Center
Resource Type: Journal article
Publication Details: Developmental cell, Vol.56(20), pp.2808-2825.e10
DOI: 10.1016/j.devcel.2021.08.018
PMID: 34529939
PMCID: PMC8551056
NLM abbreviation: Dev Cell
ISSN: 1534-5807
eISSN: 1878-1551
Publisher: Elsevier Inc
Language: English
Date published: 10/25/2021
Academic Unit: Anatomy and Cell Biology; Surgery
Record Identifier: 9984322945702771

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