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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

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Stem Cells
Lung
Neoplasms
Epithelial Cells
Breast Neoplasms
Phenotype
Growth
Proteins

Keywords

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

Cite this

Ombrato, L., Nolan, E., Kurelac, I., Mavousian, A., Bridgeman, V. L., Heinze, I., ... 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

Metastatic-niche labelling reveals parenchymal cells with stem features. / 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.

In: Nature, Vol. 572, No. 7771, 29.08.2019, p. 603-608.

Research output: Contribution to journalArticle

Ombrato, L, Nolan, E, Kurelac, I, Mavousian, A, Bridgeman, VL, 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, vol. 572, no. 7771, pp. 603-608. https://doi.org/10.1038/s41586-019-1487-6
Ombrato L, Nolan E, Kurelac I, Mavousian A, Bridgeman VL, Heinze I et al. Metastatic-niche labelling reveals parenchymal cells with stem features. Nature. 2019 Aug 29;572(7771):603-608. https://doi.org/10.1038/s41586-019-1487-6
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. / Metastatic-niche labelling reveals parenchymal cells with stem features. In: Nature. 2019 ; Vol. 572, No. 7771. pp. 603-608.
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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.",
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T1 - Metastatic-niche labelling reveals parenchymal cells with stem features

AU - Ombrato, Luigi

AU - Nolan, Emma

AU - Kurelac, Ivana

AU - Mavousian, Antranik

AU - Bridgeman, Victoria Louise

AU - Heinze, Ivonne

AU - Chakravarty, Probir

AU - Horswell, Stuart

AU - Gonzalez-Gualda, Estela

AU - Matacchione, Giulia

AU - Weston, Anne

AU - Kirkpatrick, Joanna

AU - Husain, Ehab

AU - Speirs, Valerie

AU - Collinson, Lucy

AU - Ori, Alessandro

AU - Lee, Joo-Hyeon

AU - Malanchi, Ilaria

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PY - 2019/8/29

Y1 - 2019/8/29

N2 - 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.

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KW - Metastasis

KW - ALVEOLAR

KW - LUNG

KW - ACTIVATION

KW - NEUTROPHILS

KW - MICE

KW - MODEL

KW - EXPRESSION

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