Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression
| Autor: | Takanori Oyama, Hiroshi Tazawa, Hiroshi Nouso, Yasuo Urata, Takuo Noda, Toshiyoshi Fujiwara, Morimichi Tani, Terutaka Tanimoto, Takeshi Ieda, Shunsuke Kagawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Telomerase lcsh:RC254-282 Article 03 medical and health sciences neuroblastoma 0302 clinical medicine Neuroblastoma MYCN medicine E2F1 Pharmacology (medical) Telomerase reverse transcriptase neoplasms Chemistry adenovirus medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oncolytic virus 030104 developmental biology Oncology Viral replication Cell culture 030220 oncology & carcinogenesis Cancer research Molecular Medicine biological phenomena cell phenomena and immunity hTERT N-Myc |
| Zdroj: | Molecular Therapy: Oncolytics, Vol 18, Iss, Pp 14-23 (2020) Molecular Therapy Oncolytics |
| ISSN: | 2372-7705 |
| Popis: | Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. High-risk NB is characterized by MYCN amplification and human telomerase reverse transcriptase (hTERT) rearrangement, contributing to hTERT activation and a poor outcome. For targeting hTERT-activated tumors, we developed two oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in which the hTERT promoter drives expression of the viral E1 gene for tumor-specific virus replication. In this study, we demonstrate the therapeutic potential of the hTERT-driven oncolytic adenoviruses OBP-301 and OBP-702 using four human MYCN-amplified NB cell lines (IMR-32, CHP-134, NB-1, LA-N-5) exhibiting high hTERT expression. OBP-301 and OBP-702 exhibited a strong antitumor effect in association with autophagy in NB cells. Virus-mediated activation of E2F1 protein suppressed MYCN expression. OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein. Graphical Abstract MYCN-amplified neuroblastoma (NB) cells exhibit transcriptional activation of human telomerase reverse transcriptase (hTERT) expression. hTERT promoter-driven oncolytic adenoviruses OBP-301 and OBP-702 exhibited a strong antitumor effect in human MYCN-amplified NB cells via induction of autophagy and E2F1-mediated MYCN suppression. |
| Databáze: | OpenAIRE |
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