Authors
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
Publication date
2021/10/25
Journal
Developmental cell
Volume
56
Issue
20
Pages
2808-2825. e10
Publisher
Elsevier
Description
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 …
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