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

Fernández Moro, Carlos ; Geyer, Natalie ; Harrizi, Sara ; Hamidi, Yousra ; Söderqvist, Sara ; Kuznyecov, Danyil LU ; Tidholm Qvist, Evelina ; Salmonson Schaad, Media ; Hermann, Laura and Lindberg, Amanda , et al. (2023) In Nature Communications 14(1).
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Mice, Liver Neoplasms, Hepatocytes, Aggression, Clinical Relevance
in
Nature Communications
volume
14
issue
1
article number
5024
publisher
Nature Publishing Group
external identifiers
  • pmid:37596278
  • scopus:85168381086
ISSN
2041-1723
DOI
10.1038/s41467-023-40688-x
language
English
LU publication?
no
additional info
© 2023. Springer Nature Limited.
id
6a6209f5-3d3b-4354-b8ce-f7e854d77823
date added to LUP
2023-09-14 12:01:43
date last changed
2024-06-15 08:25:51
@article{6a6209f5-3d3b-4354-b8ce-f7e854d77823,
  abstract     = {{<p>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.</p>}},
  author       = {{Fernández Moro, Carlos and Geyer, Natalie and Harrizi, Sara and Hamidi, Yousra and Söderqvist, Sara and Kuznyecov, Danyil and Tidholm Qvist, Evelina and Salmonson Schaad, Media and Hermann, Laura and Lindberg, Amanda and Heuchel, Rainer L and Martín-Bernabé, Alfonso and Dhanjal, Soniya and Navis, Anna C and Villard, Christina and Del Valle, Andrea C and Bozóky, Lorand and Sparrelid, Ernesto and Dirix, Luc and Strell, Carina and Östman, Arne and Schmierer, Bernhard and Vermeulen, Peter B and Engstrand, Jennie and Bozóky, Béla and Gerling, Marco}},
  issn         = {{2041-1723}},
  keywords     = {{Animals; Mice; Liver Neoplasms; Hepatocytes; Aggression; Clinical Relevance}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver}},
  url          = {{http://dx.doi.org/10.1038/s41467-023-40688-x}},
  doi          = {{10.1038/s41467-023-40688-x}},
  volume       = {{14}},
  year         = {{2023}},
}