| 研究実績の概要 |
High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new
therapeutic strategies are urgently needed. Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated. We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression. Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment
resistance of high-grade chondrosarcoma.
Vares, G., Ahire, V., Sunada, S., Kim, E. H., Sai, S., Chevalier, F., Romeo, PH, Yamamoto, T, Nakajima, T & Saintigny, Y. (2020). A multimodal
treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells. Radiotherapy
and Oncology, 150, 253-261.
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