美国纪念斯隆·凯特琳癌症中心Tuomas Tammela、麻省理工学院和哈佛大学Aviv Regev和麻省理工学院Tyler Jacks研究组合作取得一项新成果。他们发现在肺癌进展过程中出现了高塑性的细胞。这一研究成果在线发表在2020年7月23日的《癌细胞》上。

研究人员对基因工程小鼠肺部肿瘤从肿瘤性增生前到腺癌七个阶段进行了单细胞转录组分析。转录状态的多样性随时间增加，并且在肿瘤和小鼠之间可再现。癌细胞逐渐获取其他细胞谱系的特征，通过计算预测，研究人员证实该特征是通过常见的过渡性高可塑性细胞状态（HPCS）实现的。

因此，从小鼠肿瘤和人类患者来源的异种移植物中分离的HPCS细胞具有高度分化性和增殖能力。HPCS进程与癌症患者的不良预后有关，并证明这与小鼠化疗抗性相关。 该研究揭示了支持肿瘤内异质性的核心法则并促进针对HPCS的靶向治疗。

附：英文原文

Title: Emergence of a High-Plasticity Cell State during Lung Cancer Evolution

Author: Nemanja Despot Marjanovic, Matan Hofree, Jason E. Chan, David Canner, Katherine Wu, Marianna Trakala, Griffin G. Hartmann, Olivia Smith, Jonathan Kim, Kelly Victoria Evans, Anna Hudson, Orr Ashenberg, Caroline B.M. Porter, Alborz Bejnood, Ayshwarya Subramanian, Kenneth Pitter, Yan Yan, Toni Delroy, Devan R. Phillips, Nisargbhai Shah, Ojasvi Chaudhary, Alexander Tsankov, Travis Hollmann, Natasha Rekhtman, Pierre P. Massion, John T. Poirier, Linas Mazutis, Ruifang Li, Joo-Hyeon Lee, Angelika Amon, Charles M. Rudin, Tyler Jacks, Aviv Regev, Tuomas Tammela

Issue&Volume: 2020-07-23

Abstract: Tumor evolution from a single cell into a malignant, heterogeneous tissue remainspoorly understood. Here, we profile single-cell transcriptomes of genetically engineeredmouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma.The diversity of transcriptional states increases over time and is reproducible acrosstumors and mice. Cancer cells progressively adopt alternate lineage identities, computationallypredicted to be mediated through a common transitional, high-plasticity cell state(HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and humanpatient-derived xenografts display high capacity for differentiation and proliferation.The HPCS program is associated with poor survival across human cancers and demonstrateschemoresistance in mice. Our study reveals a central principle underpinning intra-tumoralheterogeneity and motivates therapeutic targeting of the HPCS.

DOI: 10.1016/j.ccell.2020.06.012

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30316-0