| Autor: |
Jost Luenstedt, Fabian Hoping, Reinhild Feuerstein, Bernhard Mauerer, Christopher Berlin, Julian Rapp, Lisa Marx, Wilfried Reichardt, Dominik von Elverfeldt, Dietrich Alexander Ruess, Dorothea Plundrich, Claudia Laessle, Andreas Jud, Hannes Philipp Neeff, Philipp Anton Holzner, Stefan Fichtner-Feigl, Rebecca Kesselring |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2024.1388272 |
| Popis: |
BackgroundResection 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.MethodsCRC 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.ResultsMice 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 de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding.ConclusionsRegenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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