An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver
(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.
(Less)
- author
- publishing date
- 2023-08-18
- 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
- 2024-06-29 09:33:07
@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}}, }