ArticleScientific reports2020
Silencing of sinusoidal DDR1 reduces murine liver metastasis by colon carcinoma.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- DDR1 as a key prognostic biomarker in non-small cell lung cancer: identification, validation, and potential therapeutic implications.Frontiers in immunology · 2025Article
- [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
- Prediction of liver cancer prognosis based on immune cell marker genes.Frontiers in immunology · 2023Article
- Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment.International journal of molecular sciences · 2022Review
- Article
- A Synthetic Analog of Resveratrol Inhibits the Proangiogenic Response of Liver Sinusoidal Cells during Hepatic Metastasis.Biomolecules & therapeutics · 2022Article
- Review
- Identification of potential core genes in colorectal carcinoma and key genes in colorectal cancer liver metastasis using bioinformatics analysis.Scientific reports · 2021Article
- Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation.Biomolecules · 2021Review
- Neuropilin-1: A feasible link between liver pathologies and COVID-19.World journal of gastroenterology · 2021Review
- The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development.Cancers · 2021Review
- Immune Modulatory Properties of Collagen in Cancer.Frontiers in immunology · 2021Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver metastasis depends on the collagenous microenvironment generated by hepatic sinusoidal cells (SCs). DDR1 is an atypical collagen receptor linked to tumor progression, but whether SCs express DDR1 and its implication in liver metastasis remain unknown. Freshly isolated hepatic stellate cells (HSCs), Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs), that conform the SCs, expressed functional DDR1. HSCs expressed the largest amounts. C26 colon carcinoma secretomes increased DDR1 phosphorylation in HSCs and KCs by collagen I. Inhibition of kinase activity by DDR1-IN-1 or mRNA silencing of DDR1 reduced HSCs secretion of MMP2/9 and chemoattractant and proliferative factors for LSECs and C26 cells. DDR1-IN-1 did not modify MMP2/9 in KCs or LSECs secretomes, but decreased the enhancement of C26 migration and proliferation induced by their secretomes. Gene array showed that DDR1 silencing downregulated HSCs genes for collagens, MMPs, interleukins and chemokines. Silencing of DDR1 before tumor inoculation reduced hepatic C26 metastasis in mice. Silenced livers bore less tumor foci than controls. Metastatic foci in DDR1 silenced mice were smaller and contained an altered stroma with fewer SCs, proliferating cells, collagen and MMPs than foci in control mice. In conclusion, hepatic DDR1 promotes C26 liver metastasis and favors the pro-metastatic response of SCs to the tumor.
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