PTEN公司
生物
体细胞
癌症的体细胞进化
癌症研究
表位
细胞
癌细胞
遗传异质性
表型
肿瘤进展
肿瘤异质性
癌症
细胞生物学
遗传学
PI3K/AKT/mTOR通路
抗原
信号转导
基因
作者
Xavier Rovira-Clavé,Alexandros P. Drainas,Sizun Jiang,Yunhao Bai,Maya Baron,Bokai Zhu,Alec E. Dallas,Myung Chang Lee,Theresa P. Chu,Alessandra Holzem,Ramya Ayyagari,Debadrita Bhattacharya,Erin McCaffrey,Noah F. Greenwald,Maxim Markovic,Garry L. Coles,Michael Angelo,Michael C. Bassik,Julien Sage,Garry P. Nolan
出处
期刊:Cancer Cell
[Elsevier]
日期:2022-11-01
卷期号:40 (11): 1423-1439.e11
被引量:13
标识
DOI:10.1016/j.ccell.2022.09.014
摘要
Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are still largely unsuitable to accurately track phenotypes and clonal evolution within tumors, especially in response to genetic manipulations. Here, we developed epitopes for imaging using combinatorial tagging (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI) for in situ tracking of barcodes within tissue microenvironments. Using EpicMIBI, we dissected the spatial component of cell lineages and phenotypes in xenograft models of small cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of clonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in these models. In a tumor model harboring a fraction of PTEN-deficient cancer cells, we observed a non-autonomous increase of clonal patch size in PTEN wild-type cancer cells. EpicMIBI facilitates in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity.
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