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Neutrophils escort circulating tumour cells to enable cell cycle progression

Author

Listed:
  • Barbara Maria Szczerba

    (University of Basel and University Hospital Basel)

  • Francesc Castro-Giner

    (University of Basel and University Hospital Basel
    SIB Swiss Institute of Bioinformatics)

  • Marcus Vetter

    (University Hospital Basel
    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
    ETH Zurich)

  • Christian Beisel

    (ETH Zurich)

  • Christian Kurzeder

    (University Hospital Basel
    University of Basel and 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
    ETH Zurich)

  • Nicola Aceto

    (University of Basel and University Hospital Basel)

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.

Suggested Citation

  • 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, 2019. "Neutrophils escort circulating tumour cells to enable cell cycle progression," Nature, Nature, vol. 566(7745), pages 553-557, February.
  • Handle: RePEc:nat:nature:v:566:y:2019:i:7745:d:10.1038_s41586-019-0915-y
    DOI: 10.1038/s41586-019-0915-y
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    Citations

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    Cited by:

    1. Marianna Ioannou & Dennis Hoving & Iker Valle Aramburu & Mia I. Temkin & Nathalia M. Vasconcelos & Theodora-Dorita Tsourouktsoglou & Qian Wang & Stefan Boeing & Robert Goldstone & Spyros Vernardis & V, 2022. "Microbe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening," Nature Communications, Nature, vol. 13(1), pages 1-24, December.
    2. Maria J. Garcia-Leon & Cristina Liboni & Vincent Mittelheisser & Louis Bochler & Gautier Follain & Clarisse Mouriaux & Ignacio Busnelli & Annabel Larnicol & Florent Colin & Marina Peralta & Naël Osman, 2024. "Platelets favor the outgrowth of established metastases," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Xiang Xia & Zizhen Zhang & Chunchao Zhu & Bo Ni & Shuchang Wang & Shuofei Yang & Fengrong Yu & Enhao Zhao & Qing Li & Gang Zhao, 2022. "Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Jing Wang & Ramon Ocadiz-Ruiz & Matthew S. Hall & Grace G. Bushnell & Sophia M. Orbach & Joseph T. Decker & Ravi M. Raghani & Yining Zhang & Aaron H. Morris & Jacqueline S. Jeruss & Lonnie D. Shea, 2023. "A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Charlotte R. Bell & Victoria S. Pelly & Agrin Moeini & Shih-Chieh Chiang & Eimear Flanagan & Christian P. Bromley & Christopher Clark & Charles H. Earnshaw & Maria A. Koufaki & Eduardo Bonavita & Sant, 2022. "Chemotherapy-induced COX-2 upregulation by cancer cells defines their inflammatory properties and limits the efficacy of chemoimmunotherapy combinations," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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