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Metastatic-niche labelling reveals parenchymal cells with stem features

机译：转移性利基标记显示具有干细胞特征的实质细胞

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摘要

Direct investigation of the early cellular changes induced by metastatic cells within the surrounding tissue remains a challenge. Here we present a system in which metastatic cancer cells release a cell-penetrating fluorescent protein, which is taken up by neighbouring cells and enables spatial identification of the local metastatic cellular environment. Using this system, tissue cells with low representation in the metastatic niche can be identified and characterized within the bulk tissue. To highlight its potential, we applied this strategy to study the cellular environment of metastatic breast cancer cells in the lung. We report the presence of cancer-associated parenchymal cells, which exhibit stem-cell-like features, expression of lung progenitor markers, multi-lineage differentiation potential and self-renewal activity. In ex vivo assays, lung epithelial cells acquire a cancer-associated parenchymal-cell-like phenotype when co-cultured with cancer cells and support their growth. These results highlight the potential of this method as a platform for new discoveries.
机译：直接研究由周围组织内转移细胞诱导的早期细胞变化仍然是一个挑战。在这里，我们介绍了一个系统，在该系统中，转移性癌细胞释放一种可穿透细胞的荧光蛋白，该蛋白会被邻近细胞吸收，并能够对局部转移性细胞环境进行空间识别。使用该系统，可以在大块组织中鉴定和表征转移小生境中具有低表达的组织细胞。为了突出其潜力，我们应用了该策略来研究肺中转移性乳腺癌细胞的细胞环境。我们报告存在癌症相关的实质细胞，表现出干细胞样特征，肺祖细胞标记的表达，多谱系分化潜力和自我更新活动。在离体测定中，肺上皮细胞与癌细胞共培养并支持其生长时，会获得与癌症相关的实质细胞样表型。这些结果凸显了这种方法作为新发现平台的潜力。

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  • 来源
    《Nature》 |2019年第7771期|603-608|共6页
  • 作者

    Ombrato Luigi; Nolan Emma; Kurelac Ivana; Mavousian Antranik; Bridgeman Victoria Louise; Heinze Ivonne; Chakravarty Probir; Horswell Stuart; Gonzalez-Gualda Estela; Matacchione Giulia; Weston Anne; Kirkpatrick Joanna; Husain Ehab; Speirs Valerie; Collinson Lucy; Ori Alessandro; Lee Joo-Hyeon; Malanchi Ilaria;

  • 作者单位

    Francis Crick Inst, Tumour Host Interact Lab, London, England;

    Francis Crick Inst, Tumour Host Interact Lab, London, England;

    Francis Crick Inst, Tumour Host Interact Lab, London, England|Univ Bologna, Dipartimento Sci Med & Chirurg, Bologna, Italy;

    Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England;

    Francis Crick Inst, Tumour Host Interact Lab, London, England;

    Fritz Lipmann Inst, Leibniz Inst Aging, Prote Aging, Jena, Germany;

    Francis Crick Inst, Bioinformat & Biostat Unit, London, England;

    Francis Crick Inst, Bioinformat & Biostat Unit, London, England;

    Francis Crick Inst, Tumour Host Interact Lab, London, England;

    Francis Crick Inst, Tumour Host Interact Lab, London, England;

    Francis Crick Inst, Electron Microscopy Unit, London, England;

    Fritz Lipmann Inst, Leibniz Inst Aging, Prote Aging, Jena, Germany;

    Aberdeen Royal Infirm, Dept Pathol, Aberdeen, Scotland;

    Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland;

    Francis Crick Inst, Electron Microscopy Unit, London, England;

    Fritz Lipmann Inst, Leibniz Inst Aging, Prote Aging, Jena, Germany;

    Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England|Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England;

    Francis Crick Inst, Tumour Host Interact Lab, London, England;

  • 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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