ArticleJournal of experimental & clinical cancer research : CR2021
Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Tumour-derived exosomes in liver metastasis: A Pandora's box.Cell proliferation · 2023Pooled it
- Review
- ANGPTL1 Inhibits the Growth, Migration, and Angiogenesis of Gastric Cancer Cells by Downregulating VEGFA Expression.Biochemical genetics · 2026Article
- Low SLC8A1 in Colorectal Cancer Dictates Radiotherapy Resistance Through Calcium-Dependent ANXA2Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The vascular niche: an orchestrator of the spatiotemporal dynamics of distant metastasis.Acta pharmacologica Sinica · 2026Review
- Contribution of tumor-derived extracellular vesicles in the establishment of the pre-metastatic niche: lessons learned from past experimentations and future directions.Clinical & experimental metastasis · 2026Review
- Key molecular mechanisms and regulatory networks in colorectal cancer liver metastasis.Biological procedures online · 2026Review
- Emerging insights into exosomal protein functions in colorectal cancer.Discover oncology · 2026Review
- PRL-3 up-regulates exosomal ITGαvβ5 expression to promote liver pre-metastatic niche formation and colon cancer liver metastasis.Experimental hematology & oncology · 2026Article
- Colorectal cancer liver metastases: mechanism and therapy.Frontiers in immunology · 2026Review
- Role of histone acetylation in the regulation of CD36 and ANGPTL1 in esophageal squamous cell carcinoma.BMC cancer · 2025Article
- Transcriptomic profiling of Kupffer cells exposed toFood and waterborne parasitology · 2025Article
- The hepatic macrophage: a key regulator of liver metastatic tumor microenvironment through cell crosstalk.Journal of translational medicine · 2025Review
- The Spatial Atlas of Human Anatomy (SAHA): A Multimodal Subcellular-Resolution Reference Across Human Organs.bioRxiv : the preprint server for biology · 2025Article
- Machine learning analysis of coagulation-related genes for breast cancer diagnosis and prognosis prediction.Scientific reports · 2025Article
- New insights into extracellular vesicles in metastatic cancer: From mechanisms to diagnostics and targeted therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Extracellular vesicles in colorectal cancer.Annals of coloproctology · 2025Review
- Correction: Zhang et al. Circular Nucleic Acids Act as an Oncogenic MicroRNA Sponge to Inhibit Hepatocellular Carcinoma Progression.Biomedicines · 2025Article
- Identification of potential molecular targets of luteolin in the treatment of hepatocellular carcinoma based on network pharmacology and transcriptome sequencing technology.Discover oncology · 2025Article
- Macrophages in the premetastatic and metastatic niche: key functions and therapeutic directions.Journal of translational medicine · 2025Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAngiopoietin-like protein 1 (ANGPTL1) has been proved to suppress tumor metastasis in several cancers. However, its extracellular effects on the pre-metastatic niches (PMNs) are still unclear. ANGPTL1 has been identified in exosomes, while its function remains unknown. This study was designed to explore the role of exosomal ANGPTL1 on liver metastasis in colorectal cancer (CRC).
methodsExosomes were isolated by ultracentrifugation. The ANGPTL1 level was detected in exosomes derived from human CRC tissues. The effects of exosomal ANGPTL1 on CRC liver metastasis were explored by the intrasplenic injection mouse model. The liver PMN was examined by vascular permeability assays. Exosomal ANGPTL1 localization was validated by exosome labeling. The regulatory mechanisms of exosomal ANGPTL1 on Kupffer cells were determined by RNA sequencing. qRT-PCR, Western Blot, and ELISA analysis were conducted to examine gene expressions at mRNA and protein levels.
resultsANGPTL1 protein level was significantly downregulated in the exosomes derived from CRC tumors compared with paired normal tissues. Besides, exosomal ANGPTL1 attenuated liver metastasis and impeded vascular leakiness in the liver PMN. Moreover, exosomal ANGPTL1 was mainly taken up by KCs and regulated the KCs secretion pattern, enormously decreasing the MMP9 expression, which finally prevented the liver vascular leakiness. In mechanism, exosomal ANGPTL1 downregulated MMP9 level in KCs by inhibiting the JAK2-STAT3 signaling pathway.
conclusionsTaken together, exosomal ANGPTL1 attenuated CRC liver metastasis and impeded vascular leakiness in the liver PMN by reprogramming the Kupffer cell and decreasing the MMP9 expression. This study suggests a suppression role of exosomal ANGPTL1 on CRC liver metastasis and expands the approach of ANGPTL1 functioning.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.