Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation - Archive ouverte HAL Access content directly
Journal Articles Developmental Cell Year : 2021

Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation

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Nathaniel R Campbell
  • Function : Author
Anjali Rao
  • Function : Author
Miranda V Hunter
  • Function : Author
Magdalena K Sznurkowska
  • Function : Author
Luzia Briker
  • Function : Author
Maomao Zhang
  • Function : Author
Maayan Baron
  • Function : Author
Silja Heilmann
  • Function : Author
Maxime Deforet
Colin Kenny
  • Function : Author
Lorenza P Ferretti
  • Function : Author
Ting-Hsiang Huang
  • Function : Author
Sarah Perlee
  • Function : Author
Manik Garg
  • Function : Author
Jérémie Nsengimana
  • Function : Author
Massimo Saini
  • Function : Author
Emily Montal
  • Function : Author
Mohita Tagore
  • Function : Author
Julia Newton-Bishop
  • Function : Author
Mark R Middleton
  • Function : Author
Pippa Corrie
  • Function : Author
David J Adams
  • Function : Author
Roy Rabbie
  • Function : Author
Nicola Aceto
  • Function : Author
Mitchell P Levesque
  • Function : Author
Robert A Cornell
  • Function : Author
Itai Yanai
  • Function : Author
Joao B Xavier
  • Function : Author
Richard M White
  • Function : Author
  • PersonId : 1162711

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.
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Dates and versions

hal-03772733 , version 1 (21-09-2022)

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Nathaniel R Campbell, Anjali Rao, Miranda V Hunter, Magdalena K Sznurkowska, Luzia Briker, et al.. Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation. Developmental Cell, 2021, 56 (20), pp.2808 - 2825.e10. ⟨10.1016/j.devcel.2021.08.018⟩. ⟨hal-03772733⟩
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