Metastatic-niche labelling reveals parenchymal cells with stem features

• Published in: Nature (London) Vol. 572; no. 7771; pp. 603 - 608
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-08-2019; Nature Publishing Group
• Subjects: 13/1; 13/100; 13/106; 13/31; 13/44; 13/51; 14/1; 14/19; 14/28; 14/34; 14/35; 14/63; 38/39; 38/44; 38/77; 631/67/322; 631/67/327; 64/110; 64/60; 82/58; Analysis; Animals; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer cells; Cell Differentiation; Cell Lineage; Cell self-renewal; Cell Tracking - methods; Coculture Techniques; Epithelial cells; Epithelial Cells - pathology; Female; Fluorescence; Genomes; Growth; Humanities and Social Sciences; Humans; Identification and classification; Labeling; Luminescent Proteins - analysis; Luminescent Proteins - chemistry; Luminescent Proteins - metabolism; Lung cancer; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Male; Metastases; Metastasis; Mice; Microscopy; multidisciplinary; Neoplasm Metastasis - immunology; Neoplasm Metastasis - pathology; Neoplastic Stem Cells - pathology; Neutrophils; Neutrophils - pathology; Organoids - pathology; Parenchymal Tissue - pathology; Phenotypes; Phosphorylation; Proteins; Red Fluorescent Protein; Science; Science (multidisciplinary); Staining and Labeling - methods; Stem Cell Niche - immunology; Stem cells; Tumor markers; Tumor Microenvironment - immunology; United Kingdom; United States > US
• DOI: 10.1038/s41586-019-1487-6
• EISSN: 1476-4687
• ISSN: 0028-0836

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.
A cell-penetrating fluorescent marker is used to label cells in the metastatic tumour microenvironment, revealing a variety of cell types including parenchymal cells with lung stem-cell characteristics.