Neutrophils escort circulating tumour cells to enable cell cycle progression

Barbara Maria Szczerba, Francesc Castro-Giner, Marcus Vetter, Ilona Krol, Sofia Gkountela, Julia Landin, Manuel C. Scheidmann, Cinzia Donato, Ramona Scherrer, Jochen Singer, Christian Beisel, Christian Kurzeder, Viola Heinzelmann-Schwarz, Christoph Rochlitz, Walter Paul Weber, Niko Beerenwinkel and Nicola Aceto ()
Additional contact information
Barbara Maria Szczerba: University of Basel and University Hospital Basel
Francesc Castro-Giner: University of Basel and University Hospital Basel
Marcus Vetter: University Hospital Basel
Ilona Krol: University of Basel and University Hospital Basel
Sofia Gkountela: University of Basel and University Hospital Basel
Julia Landin: University Hospital Basel
Manuel C. Scheidmann: University of Basel and University Hospital Basel
Cinzia Donato: University of Basel and University Hospital Basel
Ramona Scherrer: University of Basel and University Hospital Basel
Jochen Singer: SIB Swiss Institute of Bioinformatics
Christian Beisel: ETH Zurich
Christian Kurzeder: University Hospital Basel
Viola Heinzelmann-Schwarz: University Hospital Basel
Christoph Rochlitz: University Hospital Basel
Walter Paul Weber: University of Basel and University Hospital Basel
Niko Beerenwinkel: SIB Swiss Institute of Bioinformatics
Nicola Aceto: University of Basel and University Hospital Basel

Nature, 2019, vol. 566, issue 7745, 553-557

Abstract: Abstract A better understanding of the features that define the interaction between cancer cells and immune cells is important for the development of new cancer therapies1. However, focus is often given to interactions that occur within the primary tumour and its microenvironment, whereas the role of immune cells during cancer dissemination in patients remains largely uncharacterized2,3. Circulating tumour cells (CTCs) are precursors of metastasis in several types of cancer4–6, and are occasionally found within the bloodstream in association with non-malignant cells such as white blood cells (WBCs)7,8. The identity and function of these CTC-associated WBCs, as well as the molecular features that define the interaction between WBCs and CTCs, are unknown. Here we isolate and characterize individual CTC-associated WBCs, as well as corresponding cancer cells within each CTC–WBC cluster, from patients with breast cancer and from mouse models. We use single-cell RNA sequencing to show that in the majority of these cases, CTCs were associated with neutrophils. When comparing the transcriptome profiles of CTCs associated with neutrophils against those of CTCs alone, we detect a number of differentially expressed genes that outline cell cycle progression, leading to more efficient metastasis formation. Further, we identify cell–cell junction and cytokine–receptor pairs that define CTC–neutrophil clusters, representing key vulnerabilities of the metastatic process. Thus, the association between neutrophils and CTCs drives cell cycle progression within the bloodstream and expands the metastatic potential of CTCs, providing a rationale for targeting this interaction in treatment of breast cancer.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41586-019-0915-y Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:566:y:2019:i:7745:d:10.1038_s41586-019-0915-y

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-0915-y

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().