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黑色素瘤中的一种细胞等级解偶联生长和转移
2022-09-25 16:35

近日,比利时癌症生物学中心Jean-Christophe Marine、德国埃森大学医院Florian Rambow等研究人员合作发现,黑色素瘤中的一种细胞等级解偶联生长和转移。这一研究成果于2022年9月21日在线发表在国际学术期刊《自然》上。

通过结合小鼠遗传学、单细胞和空间转录组学、系谱追踪和定量建模,研究人员提供了肿瘤生长等级模型的证据,它反映了胚胎神经嵴细胞命运特化和分化的细胞和分子逻辑。研究人员表明,致瘤能力与空间定位的血管周围生态环境有关,这种表型是通过内皮细胞建立的细胞间交流途径获得的。与只有一部分细胞注定要促进生长的模型一致,对具有间充质样状态的黑色素瘤细胞群进行的时间性单细胞追踪显示,这些细胞并没有促进原发性肿瘤的生长,而是构成了一个转移性起始细胞库,在传播到第二器官时转换细胞身份。

这些数据提供了黑色素瘤细胞状态多样性和轨迹的空间和时间解析图,并表明支持生长和转移的能力仅限于不同的细胞池。观察到这些表型能力可以在暴露于特定的生态环境信号后动态地获得,这就需要制定治疗策略来干扰这种微环境线索的癌细胞重编程活动。

据了解,尽管黑色素瘤因其高度的异质性和可塑性而臭名昭著,但人们对细胞状态多样性的起源和程度仍然知之甚少。同样,目前还不清楚黑色素瘤的生长和转移性传播是由重叠的还是不同的黑色素瘤亚群支持。

附:英文原文

Title: A cellular hierarchy in melanoma uncouples growth and metastasis

Author: Karras, Panagiotis, Bordeu, Ignacio, Pozniak, Joanna, Nowosad, Ada, Pazzi, Cecilia, Van Raemdonck, Nina, Landeloos, Ewout, Van Herck, Yannick, Pedri, Dennis, Bervoets, Greet, Makhzami, Samira, Khoo, Jia Hui, Pavie, Benjamin, Lamote, Jochen, Marin-Bejar, Oskar, Dewaele, Michael, Liang, Han, Zhang, Xingju, Hua, Yichao, Wouters, Jasper, Browaeys, Robin, Bergers, Gabriele, Saeys, Yvan, Bosisio, Francesca, van den Oord, Joost, Lambrechts, Diether, Rustgi, Anil K., Bechter, Oliver, Blanpain, Cedric, Simons, Benjamin D., Rambow, Florian, Marine, Jean-Christophe

Issue&Volume: 2022-09-21

Abstract: Although melanoma is notorious for its high degree of heterogeneity and plasticity1,2, the origin and magnitude of cell-state diversity remains poorly understood. Equally, it is unclear whether growth and metastatic dissemination are supported by overlapping or distinct melanoma subpopulations. Here, by combining mouse genetics, single-cell and spatial transcriptomics, lineage tracing and quantitative modelling, we provide evidence of a hierarchical model of tumour growth that mirrors the cellular and molecular logic underlying the cell-fate specification and differentiation of the embryonic neural crest. We show that tumorigenic competence is associated with a spatially localized perivascular niche, a phenotype acquired through an intercellular communication pathway established by endothelial cells. Consistent with a model in which only a fraction of cells are fated to fuel growth, temporal single-cell tracing of a population of melanoma cells with a mesenchymal-like state revealed that these cells do not contribute to primary tumour growth but, instead, constitute a pool of metastatic initiating cells that switch cell identity while disseminating to secondary organs. Our data provide a spatially and temporally resolved map of the diversity and trajectories of melanoma cell states and suggest that the ability to support growth and metastasis are limited to distinct pools of cells. The observation that these phenotypic competencies can be dynamically acquired after exposure to specific niche signals warrant the development of therapeutic strategies that interfere with the cancer cell reprogramming activity of such microenvironmental cues.

DOI: 10.1038/s41586-022-05242-7

Source: https://www.nature.com/articles/s41586-022-05242-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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