التفاصيل البيبلوغرافية
| العنوان: |
Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation. |
| المؤلفون: |
Campbell, Nathaniel R.1,2,3 (AUTHOR), Rao, Anjali4 (AUTHOR), Hunter, Miranda V.3 (AUTHOR), Sznurkowska, Magdalena K.5 (AUTHOR), Briker, Luzia6 (AUTHOR), Zhang, Maomao1,3 (AUTHOR), Baron, Maayan4 (AUTHOR), Heilmann, Silja1,2 (AUTHOR), Deforet, Maxime1,2 (AUTHOR), Kenny, Colin7 (AUTHOR), Ferretti, Lorenza P.6,8 (AUTHOR), Huang, Ting-Hsiang3 (AUTHOR), Perlee, Sarah3 (AUTHOR), Garg, Manik9 (AUTHOR), Nsengimana, Jérémie1,10 (AUTHOR), Saini, Massimo5 (AUTHOR), Montal, Emily3 (AUTHOR), Tagore, Mohita3 (AUTHOR), Newton-Bishop, Julia10 (AUTHOR), Middleton, Mark R.11 (AUTHOR) |
| المصدر: |
Developmental Cell. Oct2021, Vol. 56 Issue 20, p2808-2808. 1p. |
| مصطلحات موضوعية: |
*METASTASIS, *MELANOMA, *NEURAL crest, *CELL populations, *TRANSCRIPTION factors |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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