Metastatic-niche labelling reveals parenchymal cells with stem features

被引：150

作者：

Ombrato, Luigi ^{[1
]}

Nolan, Emma ^{[1
]}

Kurelac, Ivana ^{[1
,2
]}

Mavousian, Antranik ^{[3
]}

Bridgeman, Victoria Louise ^{[1
]}

Heinze, Ivonne ^{[4
]}

Chakravarty, Probir ^{[5
]}

Horswell, Stuart ^{[5
]}

Gonzalez-Gualda, Estela ^{[1
]}

Matacchione, Giulia ^{[1
]}

Weston, Anne ^{[6
]}

Kirkpatrick, Joanna ^{[4
]}

Husain, Ehab ^{[7
]}

Speirs, Valerie ^{[8
]}

Collinson, Lucy ^{[6
]}

Ori, Alessandro ^{[4
]}

Lee, Joo-Hyeon ^{[3
,9
]}

Malanchi, Ilaria ^{[1
]}

机构：

[1] Francis Crick Inst, Tumour Host Interact Lab, London, England

[2] Univ Bologna, Dipartimento Sci Med & Chirurg, Bologna, Italy

[3] Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England

[4] Fritz Lipmann Inst, Leibniz Inst Aging, Prote Aging, Jena, Germany

[5] Francis Crick Inst, Bioinformat & Biostat Unit, London, England

[6] Francis Crick Inst, Electron Microscopy Unit, London, England

[7] Aberdeen Royal Infirm, Dept Pathol, Aberdeen, Scotland

[8] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland

[9] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England

来源：

NATURE | 2019年 / 572卷 / 7771期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

LUNG; NEUTROPHILS; ALVEOLAR; ACTIVATION; EXPRESSION; MODEL; MICE;

D O I：

10.1038/s41586-019-1487-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：603 / +

页数：22

共 47 条

[1] A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis [J].