Metastatic-niche labelling reveals parenchymal cells with stem features

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

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Abstract

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.

Original languageEnglish
Pages (from-to)603-608
Number of pages6
JournalNature
Volume572
Issue number7771
Early online date28 Aug 2019
DOIs
Publication statusPublished - 29 Aug 2019

Keywords

  • Cancer microenvironment
  • Metastasis
  • ALVEOLAR
  • LUNG
  • ACTIVATION
  • NEUTROPHILS
  • MICE
  • MODEL
  • EXPRESSION

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  • Cite this

    Ombrato, L., Nolan, E., Kurelac, I., Mavousian, A., Bridgeman, V. L., Heinze, I., Chakravarty, P., Horswell, S., Gonzalez-Gualda, E., Matacchione, G., Weston, A., Kirkpatrick, J., Husain, E., Speirs, V., Collinson, L., Ori, A., Lee, J-H., & Malanchi, I. (2019). Metastatic-niche labelling reveals parenchymal cells with stem features. Nature, 572(7771), 603-608. https://doi.org/10.1038/s41586-019-1487-6