Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation.


Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
25 10 2021
Historique:
received: 13 10 2020
revised: 07 07 2021
accepted: 20 08 2021
pubmed: 17 9 2021
medline: 16 12 2021
entrez: 16 9 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34529939
pii: S1534-5807(21)00677-8
doi: 10.1016/j.devcel.2021.08.018
pmc: PMC8551056
mid: NIHMS1737985
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2808-2825.e10

Subventions

Organisme : NCI NIH HHS
ID : U54 CA137788
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA083115
Pays : United States
Organisme : Cancer Research UK
ID : C8216/A6129
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : F30 CA220954
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Medical Research Council
ID : MR/M019012/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C588/A19167
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : K00 CA223016
Pays : United States
Organisme : Cancer Research UK
ID : 8466
Pays : United Kingdom
Organisme : NIAMS NIH HHS
ID : R01 AR062547
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229215
Pays : United States
Organisme : NCI NIH HHS
ID : DP2 CA186572
Pays : United States
Organisme : Cancer Research UK
ID : C7535/A6408
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C2195/A8466
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U54 CA132378
Pays : United States
Organisme : Cancer Research UK
ID : C588/A10721
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V000292/1
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : T32 GM007739
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests M.R.M. receives research funding from GRAIL. D.J.A. is a paid consultant for Microbiotica and receives researching funding from Astra Zeneca and OpenTargets. M.P.L. receives research funding from Roche and Novartis. N.A. is a paid consultant for companies with an interest in liquid biopsy. R.M.W. is a paid consultant to N-of-One Therapeutics, a subsidiary of Qiagen. R.M.W. is on the Scientific Advisory Board of Consano but receives no income for this. R.M.W. receives royalty payments for the use of the casper line from Carolina Biologicals.

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Auteurs

Nathaniel R Campbell (NR)

Weill Cornell/Rockefeller Memorial Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10065, USA; Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Anjali Rao (A)

Institute for Computational Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.

Miranda V Hunter (MV)

Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Magdalena K Sznurkowska (MK)

Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland.

Luzia Briker (L)

Department of Dermatology, University of Zürich Hospital, University of Zürich, Zurich, Switzerland.

Maomao Zhang (M)

Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Maayan Baron (M)

Institute for Computational Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.

Silja Heilmann (S)

Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Maxime Deforet (M)

Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Colin Kenny (C)

Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA.

Lorenza P Ferretti (LP)

Department of Dermatology, University of Zürich Hospital, University of Zürich, Zurich, Switzerland; Department of Molecular Mechanisms of Disease, University of Zürich, Zurich, Switzerland.

Ting-Hsiang Huang (TH)

Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Sarah Perlee (S)

Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Manik Garg (M)

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, UK.

Jérémie Nsengimana (J)

Leeds Institute of Medical Research at St. James's, University of Leeds School of Medicine, Leeds, UK.

Massimo Saini (M)

Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland.

Emily Montal (E)

Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Mohita Tagore (M)

Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Julia Newton-Bishop (J)

Leeds Institute of Medical Research at St. James's, University of Leeds School of Medicine, Leeds, UK.

Mark R Middleton (MR)

Oxford NIHR Biomedical Research Centre and Department of Oncology, University of Oxford, Oxford, UK.

Pippa Corrie (P)

Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

David J Adams (DJ)

Experimental Cancer Genetics, the Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK.

Roy Rabbie (R)

Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Experimental Cancer Genetics, the Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK.

Nicola Aceto (N)

Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland.

Mitchell P Levesque (MP)

Department of Dermatology, University of Zürich Hospital, University of Zürich, Zurich, Switzerland.

Robert A Cornell (RA)

Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA.

Itai Yanai (I)

Institute for Computational Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.

Joao B Xavier (JB)

Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: xavierj@mskcc.org.

Richard M White (RM)

Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: whiter@mskcc.org.

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