Involvement of CD73 and A2B Receptor in Radiation-Induced DNA Damage Response and Cell Migration in Human Glioblastoma A172 Cells
| Autor: | Kazuki Kitabatake, Mitsutoshi Tsukimoto, Toshiyuki Kaji |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Small interfering RNA Programmed cell death Adenosine DNA Repair DNA damage Pharmaceutical Science GPI-Linked Proteins Receptor Adenosine A2B Radiation Tolerance 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine Humans Receptor 5'-Nucleotidase Pharmacology Chemistry Actin remodeling Cell migration General Medicine Chemoradiotherapy Adenosine A2 Receptor Antagonists 030104 developmental biology 030220 oncology & carcinogenesis Gene Knockdown Techniques Cancer research Radiation Induced DNA Damage Glioblastoma medicine.drug DNA Damage |
| Zdroj: | Biologicalpharmaceutical bulletin. 44(2) |
| ISSN: | 1347-5215 |
| Popis: | Glioblastoma is the most common malignant tumor of the central nervous system and is treated with a combination of surgery, radiation and chemotherapy. However, the tumor often acquires radiation resistance, which is characterized by an increased DNA damage response (DDR). Here, we show that CD73, which generates extracellular adenosine from ATP, and A2B receptor, which is activated by adenosine, are involved in the γ-radiation-induced DDR and the enhanced migration ability of human glioblastoma cell line A172. To investigate DDR, we evaluated ataxia telangiectasia mutated (ATM) activation and focus formation of histone H2A isoform γ (γH2AX) and p53-binding protein 1 (53BP1) in the nucleus of A172 cells after γ-irradiation. Antagonists of A2B receptor and CD73, or knockdown with small interfering RNA (siRNA), suppressed γ-radiation-induced DDR and promoted γ-radiation-induced cell death, as well as suppressing γ-radiation-induced cell migration and actin remodeling. These results suggest that activation of A2B receptor by extracellular adenosine generated via CD73 promotes γ-radiation-induced DDR, leading to recovery from DNA damage, and also enhances cell migration and actin remodeling. The CD73-A2B receptor pathway may be a promising target for overcoming radiation resistance and the acquisition of malignant phenotypes during radiotherapy of glioblastoma. |
| Databáze: | OpenAIRE |
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