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An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver

Author

Listed:
  • Carlos Fernández Moro

    (Karolinska Institutet
    Karolinska University Hospital
    Karolinska Institutet)

  • Natalie Geyer

    (Karolinska Institutet)

  • Sara Harrizi

    (Karolinska Institutet)

  • Yousra Hamidi

    (Karolinska Institutet)

  • Sara Söderqvist

    (Karolinska Institutet)

  • Danyil Kuznyecov

    (Skåne University Hospital)

  • Evelina Tidholm Qvist

    (Karolinska University Hospital)

  • Media Salmonson Schaad

    (Karolinska Institutet)

  • Laura Hermann

    (Karolinska Institutet)

  • Amanda Lindberg

    (Uppsala University)

  • Rainer L. Heuchel

    (Karolinska Institutet)

  • Alfonso Martín-Bernabé

    (Karolinska Institutet)

  • Soniya Dhanjal

    (Karolinska Institutet)

  • Anna C. Navis

    (Karolinska Institutet)

  • Christina Villard

    (Karolinska Institutet)

  • Andrea C. Valle

    (Karolinska Institutet)

  • Lorand Bozóky

    (Karolinska Institutet)

  • Ernesto Sparrelid

    (Karolinska Institutet, Karolinska University Hospital)

  • Luc Dirix

    (Translational Cancer Research Unit (GZA Hospitals and University of Antwerp))

  • Carina Strell

    (Uppsala University
    University of Bergen)

  • Arne Östman

    (Karolinska Institutet)

  • Bernhard Schmierer

    (Karolinska Institutet)

  • Peter B. Vermeulen

    (Translational Cancer Research Unit (GZA Hospitals and University of Antwerp))

  • Jennie Engstrand

    (Karolinska Institutet, Karolinska University Hospital)

  • Béla Bozóky

    (Karolinska University Hospital)

  • Marco Gerling

    (Karolinska Institutet
    Theme Cancer, Karolinska University Hospital, 17 176)

Abstract

A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule’s extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFRhigh stroma at the liver edge to FAPhigh stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.

Suggested Citation

  • Carlos Fernández Moro & Natalie Geyer & Sara Harrizi & Yousra Hamidi & Sara Söderqvist & Danyil Kuznyecov & Evelina Tidholm Qvist & Media Salmonson Schaad & Laura Hermann & Amanda Lindberg & Rainer L., 2023. "An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40688-x
    DOI: 10.1038/s41467-023-40688-x
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    References listed on IDEAS

    as
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