Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation

被引：45

作者：

Campbell, Nathaniel R. ^{[1
,2
,3
,15
]}

Rao, Anjali ^{[4
]}

Hunter, Miranda, V ^{[3
]}

Sznurkowska, Magdalena K. ^{[5
]}

Briker, Luzia ^{[6
]}

Zhang, Maomao ^{[3
,16
]}

Baron, Maayan ^{[4
]}

Heilmann, Silja ^{[2
,17
]}

Deforet, Maxime ^{[2
,18
]}

Kenny, Colin ^{[7
]}

Ferretti, Lorenza P. ^{[6
,8
]}

Huang, Ting-Hsiang ^{[3
]}

Perlee, Sarah ^{[3
]}

Garg, Manik ^{[9
]}

Nsengimana, Jeremie ^{[10
,19
]}

Saini, Massimo ^{[5
]}

Montal, Emily ^{[3
]}

Tagore, Mohita ^{[3
]}

Newton-Bishop, Julia ^{[10
]}

Middleton, Mark R. ^{[11
,12
]}

Corrie, Pippa ^{[13
]}

Adams, David J. ^{[14
]}

Rabbie, Roy ^{[13
,14
]}

Aceto, Nicola ^{[5
]}

Levesque, Mitchell P. ^{[6
]}

Cornell, Robert A. ^{[7
]}

Yanai, Itai ^{[4
]}

Xavier, Joao B. ^{[2
]}

White, Richard M. ^{[3
]}

机构：

[1] Weill Cornell Rockefeller Mem Sloan Kettering Tri, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Computat & Syst Biol, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet, New York, NY 10065 USA

[4] NYU, Inst Computat Med, Grossman Sch Med, New York, NY 10016 USA

[5] Swiss Fed Inst Technol, Inst Mol Hlth Sci, Dept Biol, CH-8093 Zurich, Switzerland

[6] Univ Zurich, Univ Zurich Hosp, Dept Dermatol, Zurich, Switzerland

[7] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA

[8] Univ Zurich, Dept Mol Mech Dis, Zurich, Switzerland

[9] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Hinxton, Cambs, England

[10] Univ Leeds, Leeds Inst Med Res St Jamess, Sch Med, Leeds, W Yorkshire, England

[11] Univ Oxford, Oxford NIHR Biomed Res Ctr, Oxford, England

[12] Univ Oxford, Dept Oncol, Oxford, England

[13] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Canc Ctr, Cambridge, England

[14] Wellcome Sanger Inst, Expt Canc Genet, Hinxton, Cambs, England

[15] Univ Illinois, Coll Med, Chicago, IL 60612 USA

[16] Cal Life Sci LLC, San Francisco, CA 94080 USA

[17] Univ Copenhagen, Novo Nordisk Fdn Ctr Stem Cell Biol, DK-2200 Copenhagen N, Denmark

[18] Sorbonne Univ, Inst Biol Paris Seine IBPS, Lab Jean Perrin LJP, CNRS, F-75005 Paris, France

[19] Newcastle Univ, Populat Hlth Sci Inst, Biostat Res Grp, Newcastle, NSW, Australia

来源：

DEVELOPMENTAL CELL | 2021年 / 56卷 / 20期

基金：

欧洲研究理事会; 瑞士国家科学基金会; 英国医学研究理事会;

关键词：

BREAST-CANCER METASTASIS; NEURAL CREST; IN-VIVO; DIFFERENTIATION PROGRAM; TRANSCRIPTION FACTORS; EXPRESSION; PLASTICITY; ZEBRAFISH; HETEROGENEITY; INHIBITION;

D O I：

10.1016/j.devcel.2021.08.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Melanomas can have multiple coexisting cell states, including proliferative (PRO) versus invasive (INV) sub populations 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.

引用

页码：2808 / +

页数：29

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