PAX3-FKHRまたはPAX7-FKHRキメラ遺伝子は胞巣型・混合型横紋筋肉腫の76%で陽性なのに対し胎児型では検出されず, 生存率はキメラ遺伝子陽性の胞巣型で44.2%に対してキメラ遺伝子陰性の胞巣型では75.0%と有意に高く, 胎児型の76.3%と同様だった。幹細胞マーカー発現は全ての横紋筋肉腫細胞株でCD44陽性, CD44v陰性で, CD133表出率はRh30, KYM-1, RMS-YM株では2%以下, RD株では25%で, CD133陽性細胞は抗癌剤抵抗性で免疫不全マウスにおいて高い造腫瘍能を示した。Genotypeや腫瘍幹細胞のマーカー発現に基づく新治療戦略の可能性が検討された。
Either PAX3-FKHR or PAX7-FKHR gene was positive in 76% of alveolar type rhabomyosarcoma, whereas never detected in embryonal type tumor. Survival rate was significantly lower in alveolar type cases with positive chimeric gene (44.2±7.3%) compared to those with negative chimeric gene (75.0±12.5%), which was similar to that of embryonal cases (76.3±4.9%). ALL mixed type cases were alive regardless of chimeric gene positivity. CD44, a stem cell marker, was positive in all rhabdomyosarcoma cell line examined, whereas, CD44v was negative in all the cell lines. Positivity rate of CD133 was 25% in RD cell line, whereas, less than 2% in other cell lines such as Rh30, KYM-1, RMS-YM. However, CD133 positive cells are chemotherapy resistant, and rapidly formed tumor after administrated in mice. Novel treatment strategy may be stratified according to the genotype and expression of the stem cell makers in rhabdomyosarcoma.

研究種目 : 挑戦的萌芽研究
研究期間 : 2014～2015
課題番号 : 26670766
研究分野 : 小児外科学