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

Autor: Fernández Moro C; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden.; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, 14186, Sweden.; Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 14186, Stockholm, Sweden., Geyer N; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden., Harrizi S; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden., Hamidi Y; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden., Söderqvist S; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden., Kuznyecov D; Department of Clinical Genetics, Pathology and Molecular Diagnostics, Medicinsk Service, Skåne University Hospital, 22185, Lund, Sweden., Tidholm Qvist E; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, 14186, Sweden., Salmonson Schaad M; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden., Hermann L; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden., Lindberg A; Department of Immunology, Genetics and Pathology, Uppsala University, 75185, Uppsala, Sweden., Heuchel RL; Pancreatic Cancer Research Laboratory, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 14183, Hudinge, Sweden., Martín-Bernabé A; Department of Oncology-Pathology, Karolinska Institutet, 17176, Solna, Sweden., Dhanjal S; CRISPR Functional Genomics, SciLifeLab and Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17165, Solna, Sweden., Navis AC; CRISPR Functional Genomics, SciLifeLab and Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17165, Solna, Sweden., Villard C; Department of Medicine Huddinge, Karolinska Institutet, 14183, Huddinge, Sweden., Del Valle AC; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden., Bozóky L; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden., Sparrelid E; Department of Clinical Science, Intervention and Technology, Division of Surgery, Karolinska Institutet, Karolinska University Hospital, 14152, Stockholm, Sweden., Dirix L; Translational Cancer Research Unit (GZA Hospitals and University of Antwerp), Antwerp, Belgium., Strell C; Department of Immunology, Genetics and Pathology, Uppsala University, 75185, Uppsala, Sweden.; Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, 5020, Bergen, Norway., Östman A; Department of Oncology-Pathology, Karolinska Institutet, 17176, Solna, Sweden., Schmierer B; CRISPR Functional Genomics, SciLifeLab and Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17165, Solna, Sweden., Vermeulen PB; Translational Cancer Research Unit (GZA Hospitals and University of Antwerp), Antwerp, Belgium., Engstrand J; Department of Clinical Science, Intervention and Technology, Division of Surgery, Karolinska Institutet, Karolinska University Hospital, 14152, Stockholm, Sweden., Bozóky B; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, 14186, Sweden., Gerling M; Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden. marco.gerling@ki.se.; Theme Cancer, Karolinska University Hospital, 17 176, Solna, Sweden. marco.gerling@ki.se.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Aug 18; Vol. 14 (1), pp. 5024. Date of Electronic Publication: 2023 Aug 18.
DOI: 10.1038/s41467-023-40688-x
Abstrakt: 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 NGFR high stroma at the liver edge to FAP high 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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