ArticleJournal of experimental & clinical cancer research : CR2024
Tumor-derived exosomal ADAM17 promotes pre-metastatic niche formation by enhancing vascular permeability in colorectal cancer.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Mechanisms of systemic immune modulation in tumor development: Interactions across lymph nodes, bone marrow, and blood.Cancer metastasis reviews · 2026Review
- Review
- From Gut Microbiota to Hepatic Pre-Metastatic Niches: Mechanism and Translational Prospects of the Gut-Liver Axis in Regulating Colorectal Cancer Liver Metastasis.Microorganisms · 2026Review
- Expression ofInternational journal of molecular sciences · 2026Article
- Tumoral extracellular vesicles and particles reprogram interstitial macrophages in the lung to promote vascular permeability and metastasis.Nature cancer · 2026Article
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Role of NR2F2-mediated reprogramming of endothelial cells in glioblastoma progression.iScience · 2026Article
- Tumor-Derived Exosomal TAGLN2 Promotes Metastasis by Inducing Vascular Permeability and Angiogenesis via the NRP1/SEMA4D/YAP Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SPP1Cell death & disease · 2026Article
- Origin dictates function: The dual roles of exosomes derived from diverse origins in the onset and progression of colorectal cancer (Review).Oncology reports · 2026Review
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 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
- Emerging insights into exosomal protein functions in colorectal cancer.Discover oncology · 2026Review
- Nanosystem-Mediated Intercellular Crosstalk Modulation in the Tumor Microenvironment for Enhanced Cancer Immunotherapy.Drug design, development and therapy · 2026Review
- Engineering Extracellular Vesicles for Tumor Targeted Therapy: Source Optimization, Modification, and Clinical Application.International journal of nanomedicine · 2026Review
- Organ-specific pre-metastatic and metastatic niches in colorectal cancer: "discrepancy in response to immune checkpoint inhibitors in liver and lung metastasis".Frontiers in immunology · 2026Review
- Extracellular vesicles cargo orchestration in colorectal cancer: immune evasion, stromal remodeling, and therapeutic frontiers.Molecular cancer · 2025Review
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHematological metastasis has been recognized as a crucial factor contributing to the high rates of metastasis and mortality observed in colorectal cancer (CRC). Notably, exosomes derived from cancer cells participate in the formation of CRC pre-metastatic niches; however, the mechanisms underlying their effects are largely unknown. While our preliminary research revealed the role of exosome-derived disintegrin and metalloproteinase 17 (ADAM17) in the early stages of CRC metastasis, the role of exosomal ADAM17 in CRC hematogenous metastasis remains unclear.
methodsIn the present study, we isolated and purified exosomes using ultracentrifugation and identified exosomal proteins through quantitative mass spectrometry. In vitro, co-culture assays were conducted to evaluate the impact of exosomal ADAM17 on the permeability of the blood vessel endothelium. Vascular endothelial cell resistance, the cell index, membrane protein separation, flow cytometry, and immunofluorescence were employed to investigate the mechanisms underlying exosomal ADAM17-induced vascular permeability. Additionally, a mouse model was established to elucidate the role of exosomal ADAM17 in the modulation of blood vessel permeability and pre-metastatic niche formation in vivo.
resultsOur clinical data indicated that ADAM17 derived from the circulating exosomes of patients with CRC could serve as a blood-based biomarker for predicting metastasis. The CRC-derived exosomal ADAM17 targeted vascular endothelial cells, thus enhancing vascular permeability by influencing vascular endothelial cadherin cell membrane localization. Moreover, exosomal ADAM17 mediated the formation of a pre-metastatic niche in nude mice by inducing vascular leakage, thereby promoting CRC metastasis. Nonetheless, ADAM17 selective inhibitors effectively reduced CRC metastasis in vivo.
conclusionsOur results suggest that exosomal ADAM17 plays a pivotal role in the hematogenous metastasis of CRC. Thus, this protein may serve as a valuable blood-based biomarker and potential drug target for CRC metastasis intervention.
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