ArticleBMC cancer2019
Ionizing radiation increases the endothelial permeability and the transendothelial migration of tumor cells through ADAM10-activation and subsequent degradation of VE-cadherin.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 49 citations in OpenAlex.
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- Pre-Exposure Prophylaxis with Vasculotide Enhances Survival and Alleviates Hematopoietic and Gastrointestinal Injury Following Lethal Total Body Irradiation.International journal of molecular sciences · 2026Article
- Vibration-Mediated Recovery of Irradiated Osteocytes and Their Regulatory Role in Breast Cancer Bone Metastasis.Advanced healthcare materials · 2026Article
- The Protective Efficacy of Total Alkaloids from Nelumbinis Plumula on Irradiation-Induced Oxidative Stress Damage in Human Umbilical Vein Endothelial Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Application of radiotherapy-preexcited gambogic acid dual targeting nanoparticles in colorectal cancer.RSC advances · 2025Article
- Long-Term Effects of Radiation Therapy on Cerebral Microvessel Proteome: A Six Month Post-Exposure Analysis.ACS omega · 2025Article
- Circulating tumour cells for the prediction of the response to radiation therapy in prostate cancer.The British journal of radiology · 2025Review
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- Modeling the effects of radiation on the bone tumor microenvironment: opportunities for exploring combination therapies in microphysiologic systems.Cellular & molecular biology letters · 2025Review
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- CD147-high extracellular vesicles promote gastric cancer metastasis via VEGF/AKT/eNOS and AKT/mTOR pathways.Oncogenesis · 2025Article
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- The Protein Kinase A Inhibitor KT5720 Prevents Endothelial Dysfunctions Induced by High-Dose Irradiation.International journal of molecular sciences · 2024Article
- Age and dose dependent changes to the bone and bone marrow microenvironment after cytotoxic conditioning with busulfan.Frontiers in cell and developmental biology · 2024Article
- Article
- Combination of irinotecan silicasome nanoparticles with radiation therapy sensitizes immunotherapy by modulating the activation of the cGAS/STING pathway for colorectal cancer.Materials today. Bio · 2023Article
- Assessment of the Severity of Left Anterior Descending Coronary Artery Stenoses by Enhanced Transthoracic Doppler Echocardiography: Validation of a Method Based on the Continuity Equation.Diagnostics (Basel, Switzerland) · 2023Article
- 3D Cell Models in Radiobiology: Improving the Predictive Value of In Vitro Research.International journal of molecular sciences · 2023Review
- ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?International journal of molecular sciences · 2023Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe analyzed the changes in permeability of endothelial cell layers after photon irradiation, with a focus on the metalloproteases ADAM10 and ADAM17, and on VE-cadherin, components crucial for the integrity of endothelial intercellular junctions, and their roles in the transmigration of cancer cells through endothelial cell monolayers.
methodsPrimary HUVEC were irradiated with 2 or 4 Gy photons at a dose rate of 5 Gy/min. The permeability of an irradiated endothelial monolayer for macromolecules and tumor cells was analyzed in the presence or absence of the ADAM10/17 inhibitors GI254023X and GW280264X. Expression of ADAM10, ADAM17 and VE-Cadherin in endothelial cells was quantified by immunoblotting and qRT. VE-Cadherin was additionally analyzed by immunofluorescence microscopy and ELISA.
resultsIonizing radiation increased the permeability of endothelial monolayers and the transendothelial migration of tumor cells. This was effectively blocked by a selective inhibition (GI254023X) of ADAM10. Irradiation increased both, the expression and activity of ADAM10, which led to increased degradation of VE-cadherin, but also led to higher rates of VE-cadherin internalization. Increased degradation of VE-cadherin was also observed when endothelial monolayers were exposed to tumor-cell conditioned medium, similar to when exposed to recombinant VEGF.
conclusionsOur results suggest a mechanism of irradiation-induced increased permeability and transendothelial migration of tumor cells based on the activation of ADAM10 and the subsequent change of endothelial permeability through the degradation and internalization of VE-cadherin.
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