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

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. Heuchel, Alfonso Martín-Bernabé, Soniya Dhanjal, Anna C. Navis, Christina Villard, Andrea C. Valle, Lorand Bozóky, Ernesto Sparrelid, Luc Dirix, Carina Strell, Arne Östman, Bernhard Schmierer, Peter B. Vermeulen, Jennie Engstrand, Béla Bozóky and Marco Gerling ()
Additional contact information
Carlos Fernández Moro: 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
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

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-40688-x Abstract (text/html)

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:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40688-x

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

DOI: 10.1038/s41467-023-40688-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

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