Partial hepatectomy accelerates colorectal metastasis by priming an inflammatory premetastatic niche in the liver.
colorectal cancer
liver metastasis
partial hepatectomy
premetastatic niche
tight junctions
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2024
2024
Historique:
received:
19
02
2024
accepted:
27
05
2024
medline:
26
6
2024
pubmed:
26
6
2024
entrez:
26
6
2024
Statut:
epublish
Résumé
Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression. CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry. Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.
Sections du résumé
Background
UNASSIGNED
Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression.
Methods
UNASSIGNED
CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry.
Results
UNASSIGNED
Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in
Conclusions
UNASSIGNED
Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.
Identifiants
pubmed: 38919609
doi: 10.3389/fimmu.2024.1388272
pmc: PMC11196966
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1388272Informations de copyright
Copyright © 2024 Luenstedt, Hoping, Feuerstein, Mauerer, Berlin, Rapp, Marx, Reichardt, von Elverfeldt, Ruess, Plundrich, Laessle, Jud, Neeff, Holzner, Fichtner-Feigl and Kesselring.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.