EphB4 mediates resistance to antiangiogenic therapy in experimental glioma
| العنوان: | EphB4 mediates resistance to antiangiogenic therapy in experimental glioma |
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| المؤلفون: | Moritz Markel, Peter Vajkoczy, Christian Uhl, Thomas Broggini, Melina Nieminen, Irina Kremenetskaia, Marcus Czabanka |
| المصدر: | Angiogenesis |
| بيانات النشر: | Springer Netherlands, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Physiology, Angiogenesis, Clinical Biochemistry, Tumor microcirculation, Receptor, EphB4, Antiangiogenic therapy, Mice, Nude, Angiogenesis Inhibitors, Apoptosis, Glioblastoma multiforme, 03 medical and health sciences, Intravital microscopy, Mice, 0302 clinical medicine, Glioma, Cell Line, Tumor, medicine, Ephrin, Animals, Humans, Pericyte, Cell Proliferation, Original Paper, Neovascularization, Pathologic, business.industry, EphB4, Neoplasms, Experimental, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Vascular morphogenesis, Cancer research, business |
| الوصف: | Introduction Alterations in vascular morphogenesis are hallmarks of antiangiogenesis-resistant tumor vessels. Vascular morphogenesis is regulated by ephrinB2-EphB4 system which may induce different biological effects depending on the oncological and molecular contexts. It was the aim of the current study to characterize the influence of EphB4 on tumor microcirculation after antiangiogenic treatment using different SF126 glioma models. Materials and methods Using an ecotropic transfection system, empty vector (pLXSN) or EphB4 (EphB4OE) overexpressing Phoenix-ECO cells were coimplanted with SF126 glioma cells subcutaneously (dorsal skinfold chamber, DSC) and orthotopically (cranial window, CW). Tumor volume was assessed by MRI. Intravital microscopy (IVM) allowed microcirculatory analysis (total {TVD} and functional vessel density {FVD}, diameter {D}, and permeability index {PI}) before and after antiangiogenic treatment (Sunitinib: DSC: 40 mg/kg BW, 6 days; CW: 80 mg/kg BW, 4 days). Immunohistochemistry included Pecam–Desmin, Ki67, TUNEL, and Caspase 3 stainings. Results EphB4OE induced large and treatment-resistant tumor vessels (FVD: Control/Su: 110 ± 23 cm/cm2 vs. EphB4OE/Su: 103 ± 42 cm/cm2). Maintenance of pericyte–endothelial cell interactions (Control: 80 ± 12 vs. Control/Su: 47 ± 26%; EphB4OE: 88 ± 9 vs. EphB4OE/Su: 74 ± 25%) and reduced antiproliferative (Control: 637 ± 80 vs. Control/Su: 110 ± 22; EphB4OE: 298 ± 108 vs. EphB4OE/Su: 213 ± 80) and proapoptotic responses (Control: 196 ± 25 vs. Control / Su: 404 ± 60; EphB4OE: 183 ± 20 vs. EphB4OE/Su: 270 ± 66) were observed under EphB4 overexpression. Conclusion EphB4 overexpression leads to vascular resistance by altering vascular morphogenesis, pericyte coverage, and cellular proliferation/apoptosis in experimental SF126 glioma models. |
| اللغة: | English |
| تدمد: | 1573-7209 0969-6970 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c2aeba879d12b8031feb8583651e0d6Test http://europepmc.org/articles/PMC6208883Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4c2aeba879d12b8031feb8583651e0d6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15737209 09696970 |
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