ArticleScience advances2022
Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends.Frontiers in oncology · 2023Pooled it
- Review
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- Bioinspired microcapsule reactor with engineered probiotics for IBD therapy.Nature communications · 2026Article
- A Novel Zebrafish Liver-Specific Metastasis Model Reveals c-Met as a Driver of Liver Tropism.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Targeting the p38/MAPK pathway to induce apoptosis: a multidimensional mechanistic exploration of Mentha and its active compound diosmetin against liver cancer.Scientific reports · 2025Article
- SMYD3-CDCP1 Axis Drives EMT and CAF Activation in Colorectal Cancer and Is Targetable for Oxaliplatin Sensitization.Biomedicines · 2025Article
- Combination LIGHT overexpression and checkpoint blockade disrupts the tumor immune environment impacting colorectal liver metastases.Science advances · 2025Article
- Review
- Cancer Metastases to the Liver: Mechanisms of Tumor Cell Colonization.Pharmaceuticals (Basel, Switzerland) · 2024Review
- ADAMTS18-fibronectin interaction regulates the morphology of liver sinusoidal endothelial cells.iScience · 2024Article
- [The Role and Significance of Hepatic Environmental Cells in Tumor Metastatic Colonization to Liver].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Review
Corrections and comments
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Authors and funding
26 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular gap (iGap) formation in liver sinusoidal endothelial cells (LSECs) is caused by the destruction of fenestrae and appears under pathological conditions; nevertheless, their role in metastasis of cancer cells to the liver remained unexplored. We elucidated that hepatotoxin-damaged and fibrotic livers gave rise to LSECs-iGap formation, which was positively correlated with increased numbers of metastatic liver foci after intrasplenic injection of Hepa1-6 cells. Hepa1-6 cells induced interleukin-23-dependent tumor necrosis factor-α (TNF-α) secretion by LSECs and triggered LSECs-iGap formation, toward which their processes protruded to transmigrate into the liver parenchyma. TNF-α triggered depolymerization of F-actin and induced matrix metalloproteinase 9 (MMP9), intracellular adhesion molecule 1, and CXCL expression in LSECs. Blocking MMP9 activity by doxycycline or an MMP2/9 inhibitor eliminated LSECs-iGap formation and attenuated liver metastasis of Hepa1-6 cells. Overall, this study revealed that cancer cells induced LSEC-iGap formation via proinflammatory paracrine mechanisms and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver.
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