Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation.
Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation.
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DOI：
10.1016/j.devcel.2021.08.018
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发表时间：
2021-10-25
影响因子：
11.8
通讯作者：
White RM
中科院分区：
文献类型：
--
作者：
Campbell NR;Rao A;Hunter MV;Sznurkowska MK;Briker L;Zhang M;Baron M;Heilmann S;Deforet M;Kenny C;Ferretti LP;Huang TH;Perlee S;Garg M;Nsengimana J;Saini M;Montal E;Tagore M;Newton-Bishop J;Middleton MR;Corrie P;Adams DJ;Rabbie R;Aceto N;Levesque MP;Cornell RA;Yanai I;Xavier JB;White RM
黑色素瘤可以有多种共存的细胞状态，包括增殖（PRO）与侵袭（INV）亚群，代表“生存或生长”的权衡；然而，人们对这些种群之间的相互作用知之甚少。通过结合斑马鱼模型和患者样本分析，我们发现INV和PRO细胞形成空间结构的异型簇，并在转移的播种中合作，维持细胞状态的异质性。INV细胞彼此紧密地附着在一起，形成带有PRO细胞边缘的簇。活体成像显示INV细胞促进低转移性PRO细胞的传播。我们发现TFAP2神经嵴转录因子是聚类和PRO/INV状态的主要调控因子。从转移性黑色素瘤患者中分离出的簇显示出异型PRO-INV簇。我们的数据提示了这两种不同细胞群共存的框架，其中异型集群通过细胞间合作促进转移。增殖（PRO）和侵袭（INV）细胞状态共存于黑色素瘤。Campbell等人证明了PRO和INV细胞通过异型循环肿瘤细胞（CTC）集群在转移过程中相互合作，并确定TFAP2是一个关键的中介。他们的工作强调了集体传播在黑色素瘤转移中的作用。
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. 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.
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影响因子：
8.4
作者：
FIDLER, IJ
通讯作者：
FIDLER, IJ
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0606053103
发表时间：
2006-09-05
影响因子：
11.1
作者：
Axelrod, Robert;Axelrod, David E.;Pienta, Kenneth J.
通讯作者：
Pienta, Kenneth J.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.1010740107
发表时间：
2011-01-04
影响因子：
11.1
作者：
de Croze, Noemie;Maczkowiak, Frederique;Monsoro-Burq, Anne H.
通讯作者：
Monsoro-Burq, Anne H.