Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation
| Autor: | Richard M. White, Emily Montal, Maxime Deforet, Julia Newton-Bishop, Magdalena Katarzyna Sznurkowska, Mitchell P. Levesque, Mohita Tagore, Robert A. Cornell, Massimo Saini, Jérémie Nsengimana, Joao B. Xavier, Silja Heilmann, Sarah C. Perlee, Maomao Zhang, David J. Adams, Miranda V. Hunter, Manik Garg, Anjali Rao, Nicola Aceto, Nathaniel R. Campbell, Itai Yanai, Pippa Corrie, Roy Rabbie, Lorenza P. Ferretti, Colin Kenny, Luzia Briker, Mark R. Middleton, Ting-Hsiang Huang, Maayan Baron |
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| Rok vydání: | 2021 |
| Předmět: |
Cell
Cell Count Article General Biochemistry Genetics and Molecular Biology Metastasis Cell Movement medicine Humans Animals Cluster Analysis Neoplasm Metastasis Melanoma Molecular Biology Transcription factor Zebrafish biology Neural crest Master regulator Cell Biology biochemical phenomena metabolism and nutrition Intravital Imaging Neoplastic Cells Circulating biology.organism_classification medicine.disease Gene Expression Regulation Neoplastic medicine.anatomical_structure Neural Crest Cancer research Developmental Biology |
| Zdroj: | Dev Cell |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2021.08.018 |
| Popis: | Melanomas can have multiple co-existing cell states, including proliferative (PRO) versus invasive (INV) subpopulations that represent a “go or grow” tradeoff; 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. |
| Databáze: | OpenAIRE |
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