美国加州大学旧金山分校Jonathan S. Weissman等研究人员合作通过单细胞谱系揭示出异种移植癌转移的速率、途径和驱动因素。相关论文于2021年1月21日在线发表在《科学》杂志上。

研究人员应用了基于Cas9的单细胞谱系示踪来研究肺癌异种移植小鼠模型中转移的速率、途径和驱动因素。研究人员报道了在数月的生长和传播中追踪到的成千上万种癌细胞的深层系统发育。这揭示了由于基因表达中已有的和遗传的差异所引起的转移能力异质性。研究人员证明了这些已鉴定的基因可以驱动侵袭性，并发现了KRT17的意外抑制作用。

研究人员还显示，转移通过多向组织途径和复杂的播种拓扑传播。总体而言，研究人员证明了以亚克隆分辨率和大规模追踪癌症进展的实用性。

据了解，肿瘤群体的详细系统发育史可以描述癌症进展过程中关键事件（如转移性传播）的历史和时间顺序。

附：英文原文

Title: Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts

Author: Jeffrey J. Quinn, Matthew G. Jones, Ross A. Okimoto, Shigeki Nanjo, Michelle M. Chan, Nir Yosef, Trever G. Bivona, Jonathan S. Weissman

Issue&Volume: 2021/01/21

Abstract: Detailed phylogenies of tumor populations can recount the history and chronology of critical events during cancer progression, such as metastatic dissemination. We applied a Cas9-based, single-cell lineage tracer to study the rates, routes, and drivers of metastasis in a lung cancer xenograft mouse model. We report deeply resolved phylogenies for tens of thousands of cancer cells traced over months of growth and dissemination. This revealed stark heterogeneity in metastatic capacity, arising from pre-existing and heritable differences in gene expression. We demonstrate that these identified genes can drive invasiveness, and uncovered an unanticipated suppressive role for KRT17. We also show that metastases disseminated via multidirectional tissue routes and complex seeding topologies. Overall, we demonstrate the power of tracing cancer progression at subclonal resolution and vast scale.

DOI: 10.1126/science.abc1944

Source: https://science.sciencemag.org/content/early/2021/01/21/science.abc1944