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A metastasis map of human cancer cell lines

机译:人癌细胞系的转移地图

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摘要

Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical owing to the complexity of in vivo models. Here we introduce an in vivo barcoding strategy that is capable of determining the metastatic potential of human cancer cell lines in mouse xenografts at scale. We validated the robustness, scalability and reproducibility of the method and applied it to 500 cell lines~(1,2)spanning 21 types of solid tumour. We created a first-generation metastasis map (MetMap) that reveals organ-specific patterns of metastasis, enabling these patterns to be associated with clinical and genomic features. We demonstrate the utility of MetMap by investigating the molecular basis of breast cancers capable of metastasizing to the brain-a principal cause of death in patients with this type of cancer. Breast cancers capable of metastasizing to the brain showed evidence of altered lipid metabolism. Perturbation of lipid metabolism in these cells curbed brain metastasis development, suggesting a therapeutic strategy to combat the disease and demonstrating the utility of MetMap as a resource to support metastasis research.
机译:大多数来自癌症的死亡是通过转移来解释的,但由于体内模型的复杂性,但大规模的转移研究是不切实际的。在这里,我们介绍了一种体内条形码策略,其能够在规模中确定小鼠异种移植物中人类癌细胞系的转移潜力。我们验证了该方法的鲁棒性,可扩展性和再现性,并将其应用于500个细胞系〜(1,2)跨越21种固体瘤。我们创建了一种第一代转移地图(METMAP),揭示了转移的器官特异性模式,使这些模式能够与临床和基因组特征相关联。我们通过研究能够转移到大脑的乳腺癌的分子基础来证明MetMap的效用 - 这种癌症患者的主要死因。能够转移到大脑的乳腺癌显示出改变脂质代谢的证据。这些细胞在这些细胞抑制脑转移发育中的脂质代谢的扰动,暗示了对抗疾病的治疗策略,并证明MetMap的效用作为支持转移研究的资源。

著录项

  • 来源
    《Nature》 |2020年第7837期|331-336|共6页
  • 作者单位

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard|Koch Institute for Integrative Cancer Research Department of Biology Massachusetts Institute of Technology;

    Edwin L. Steele Laboratories Department of Radiation Oncology Massachusetts General Hospital;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard;

    Institute for Medical Engineering and Science Picower Institute for Learning and Memory Department of Chemical Engineering Massachusetts Institute of Technology;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard|Institute for Medical Engineering and Science Picower Institute for Learning and Memory Department of Chemical Engineering Massachusetts Institute of Technology;

    Edwin L. Steele Laboratories Department of Radiation Oncology Massachusetts General Hospital|Harvard Medical School;

    Broad Institute of MIT and Harvard;

    Broad Institute of MIT and Harvard|Koch Institute for Integrative Cancer Research Department of Biology Massachusetts Institute of Technology|Dana-Farber Cancer Institute;

    Broad Institute of MIT and Harvard|Harvard Medical School|Dana-Farber Cancer Institute;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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