ArticleCancer research communications2021
The ADAM17-directed Inhibitory Antibody MEDI3622 Antagonizes Radiotherapy-induced VEGF Release and Sensitizes Non-Small Cell Lung Cancer for Radiotherapy.
Article in Cancer research communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy.Nature communications · 2024Article
- Genetic Predisposition to Elevated Levels of Circulating ADAM17 Is Associated with the Risk of Severe COVID-19.International journal of molecular sciences · 2023Article
- Human Non-Small Cell Lung Cancer-Chicken Embryo Chorioallantoic Membrane Tumor Models for Experimental Cancer Treatments.International journal of molecular sciences · 2023Article
- Homogenous TP53mut-associated tumor biology across mutation and cancer types revealed by transcriptome analysis.Cell death discovery · 2023Article
- The role of EphA2 in ADAM17- and ionizing radiation-enhanced lung cancer cell migration.Frontiers in oncology · 2023Article
- Immunomodulatory role of metalloproteinase ADAM17 in tumor development.Frontiers in immunology · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cellular response to ionizing radiation (IR) depends on tumor cell and microenvironmental factors. Here, we investigated the role of IR-induced ADAM17 matrix metalloproteinase activity for the intercellular communication between tumor cells and the tumor vasculature in non-small cell lung cancer (NSCLC) tumor models. Factors shed by ADAM17 from NSCLC tumor cells (A549, H358) and relevant for endothelial cell migration were investigated using transwell migration assays, ELISA, and flow cytometry. Tumor angiogenesis-related endpoints were analyzed with the chorio-allantoic membrane assay and in murine NSCLC tumor models. Efficacy-oriented experiments were performed in a murine orthotopic NSCLC tumor model using irradiation with an image-guided small-animal radiotherapy platform alone and in combination with the novel ADAM17-directed antibody MEDI3622. Significance: The tumor response to radiotherapy is influenced by several factors of the tumor microenvironment. We demonstrate that inhibition of the sheddase ADAM17 by the novel antibody MEDI3622 reduces IR-induced VEGF release from tumor cells relevant for endothelial cell migration and vasculature protection, thereby enhancing radiotherapy treatment outcome of NSCLC.
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