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 () and Ilaria Malanchi ()
Additional contact information
Luigi Ombrato: The Francis Crick Institute
Emma Nolan: The Francis Crick Institute
Ivana Kurelac: The Francis Crick Institute
Antranik Mavousian: University of Cambridge
Victoria Louise Bridgeman: The Francis Crick Institute
Ivonne Heinze: Leibniz Institute on Aging, Fritz Lipmann Institute (FLI)
Probir Chakravarty: The Francis Crick Institute
Stuart Horswell: The Francis Crick Institute
Estela Gonzalez-Gualda: The Francis Crick Institute
Giulia Matacchione: The Francis Crick Institute
Anne Weston: The Francis Crick Institute
Joanna Kirkpatrick: Leibniz Institute on Aging, Fritz Lipmann Institute (FLI)
Ehab Husain: Aberdeen Royal Infirmary
Valerie Speirs: University of Aberdeen
Lucy Collinson: The Francis Crick Institute
Alessandro Ori: Leibniz Institute on Aging, Fritz Lipmann Institute (FLI)
Joo-Hyeon Lee: University of Cambridge
Ilaria Malanchi: The Francis Crick Institute

Nature, 2019, vol. 572, issue 7771, 603-608

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1487-6

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