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

doi:10.1038/s41586-019-1487-6

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

Medical Sciences

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	603-608
Number of pages	6
Journal	Nature
Volume	572
Issue number	7771
Early online date	28 Aug 2019
DOIs	https://doi.org/10.1038/s41586-019-1487-6 https://doi.org/10.1038/s41586-019-1697-y
Publication status	Published - 29 Aug 2019

Bibliographical note

We thank E. Sahai, P. Scaffidi (The Francis Crick Institute) and V. Sanz-Moreno (Barts Cancer Institute) for scientific discussions, critical reading of the manuscript and sharing cell lines and mouse strains; M. Izquierdo (CSIC, Madrid) for sharing the CD63–GFP plasmid; E. Nye and the pathologists G. Stamp and E. Herbert from the Experimental Histopathology Unit at the Francis Crick Institute for histological processing and analysis support; J. Bee from the Biological Resources Unit at the Francis Crick Institute for technical support with mice and mouse tissues; R. Goldstone and A. Edwards from the Advanced Sequencing Facility at the Francis Crick Institute for technical support; M. Llorian-Sopena from the Bioinformatics and Biostatistics Unit at the Francis Crick Institute for helping with the RNA sequencing analysis; the Flow Cytometry Unit at the Francis Crick Institute, particularly S. Purewal and J. Cerveira, for invaluable technical help; the Cell Services Unit at the Francis Crick Institute; C. Moore (The Francis Crick Institute) for intra-tracheal injections; and I. Pshenichnaya, P. Humphreys, S. McCallum and Cambridge Stem Cell Institute core facilities for technical assistance. We acknowledge support from the FLI Core Facility Proteomics, which is a member of the Leibniz Association and is financially supported by the Federal Government of Germany and the State of Thuringia. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001112), the UK Medical Research Council (FC001112), and the Wellcome Trust (FC001112) and the European Research Council grant (ERC CoG-H2020-725492); and by the Wellcome Trust—MRC Stem Cell Institute, which receives funding from the Sir Henry Dale Fellowship from Wellcome, the Royal Society (107633/Z/15/Z) and the European Research Council Starting Grant (679411).

Author Correction: Metastatic-niche labelling reveals parenchymal cells with stem features (Nature, (2019), 572, 7771, (603-608), 10.1038/s41586-019-1487-6)
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, 2019, vol. 575, issue 7784, p. E8. Nature http://dx.doi.org/10.1038/s41586-019-1697-y

Keywords

Cancer microenvironment
Metastasis
ALVEOLAR
LUNG
ACTIVATION
NEUTROPHILS
MICE
MODEL
EXPRESSION

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41586-019-1487-6Licence: Unspecified
10.1038/s41586-019-1697-y

Ombrato_et_al_Nature_AAMAccepted author manuscript, 3.76 MBLicence: Other

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, https://doi.org/10.1038/s41586-019-1697-y

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, https://doi.org/10.1038/s41586-019-1697-y

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title = "Metastatic-niche labelling reveals parenchymal cells with stem features",

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

note = "We thank E. Sahai, P. Scaffidi (The Francis Crick Institute) and V. Sanz-Moreno (Barts Cancer Institute) for scientific discussions, critical reading of the manuscript and sharing cell lines and mouse strains; M. Izquierdo (CSIC, Madrid) for sharing the CD63–GFP plasmid; E. Nye and the pathologists G. Stamp and E. Herbert from the Experimental Histopathology Unit at the Francis Crick Institute for histological processing and analysis support; J. Bee from the Biological Resources Unit at the Francis Crick Institute for technical support with mice and mouse tissues; R. Goldstone and A. Edwards from the Advanced Sequencing Facility at the Francis Crick Institute for technical support; M. Llorian-Sopena from the Bioinformatics and Biostatistics Unit at the Francis Crick Institute for helping with the RNA sequencing analysis; the Flow Cytometry Unit at the Francis Crick Institute, particularly S. Purewal and J. Cerveira, for invaluable technical help; the Cell Services Unit at the Francis Crick Institute; C. Moore (The Francis Crick Institute) for intra-tracheal injections; and I. Pshenichnaya, P. Humphreys, S. McCallum and Cambridge Stem Cell Institute core facilities for technical assistance. We acknowledge support from the FLI Core Facility Proteomics, which is a member of the Leibniz Association and is financially supported by the Federal Government of Germany and the State of Thuringia. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001112), the UK Medical Research Council (FC001112), and the Wellcome Trust (FC001112) and the European Research Council grant (ERC CoG-H2020-725492); and by the Wellcome Trust—MRC Stem Cell Institute, which receives funding from the Sir Henry Dale Fellowship from Wellcome, the Royal Society (107633/Z/15/Z) and the European Research Council Starting Grant (679411). Author Correction: Metastatic-niche labelling reveals parenchymal cells with stem features (Nature, (2019), 572, 7771, (603-608), 10.1038/s41586-019-1487-6) 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, 2019, vol. 575, issue 7784, p. E8. Nature http://dx.doi.org/10.1038/s41586-019-1697-y",

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AU - Heinze, Ivonne

AU - Chakravarty, Probir

AU - Horswell, Stuart

AU - Gonzalez-Gualda, Estela

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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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Metastatic-niche labelling reveals parenchymal cells with stem features

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Valerie Speirs

Amnis ImageStream-X MarkII (ISX MKII)- Dual Camera System with Autosampler

BD Influx Cell Sorter

BD LSR Fortessa

Cite this

Metastatic-niche labelling reveals parenchymal cells with stem features

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Profiles

Valerie Speirs

Equipment

Amnis ImageStream-X MarkII (ISX MKII)- Dual Camera System with Autosampler

BD Influx Cell Sorter

BD LSR Fortessa

Cite this