日本質量分析学会 第66回質量分析総合討論会

プログラム

オーラルセッション

第4日 5月18日(金) 15:45~16:05 A会場(オービットホール)

卵巣明細胞癌における新規バイオマーカーLeftyの同定とその発現意義

(1北里大医2理研IMS3北里大理)
o松本俊英1秋谷昌史1川島祐介2小寺義男3横井愛香1小栗康子1橋村美紀1三枝信1

Ovarian clear cell carcinoma (OCCCa) shows chemoresistance and clinical outcomes at advanced stages are generally unfavorable. To identify proteins involved in OCCCa, shotgun proteomics analysis was applied using formalin-fixed and paraffin-embedded samples. Of the highly expressed proteins in OCCCa, we focused on left-right determination factor (LEFTY). In 143 cases of ovarian epithelial carcinoma, LEFTY expression at both mRNA and protein levels was significantly higher in OCCCas compared with non-OCCCas. OCCCa cell lines treated with TGF-β1, underwent morphological changes toward an EMT appearance, along with increased expression of LEFTY and Snail. The cells also showed CSC properties, as demonstrated by increases in ALDH1high activity population, number of spheroid formation, and expression of several CSC markers. Inhibition of LEFTY expression induced decreases in the number of spindle-shaped cells and CSC features, while cells stably overexpressing LEFTY exhibited enhancement of such EMT/CSC properties. Finally, treatment of cells with TGF-β1 led to increased LEFTY expression and activation of Akt, which subsequently induced inactivation of GSK-3β, while inhibition of GSK-3β resulted in increased expression of both LEFTY and Snail. In conclusion, LEFTY maybe an excellent OCCCa-specific molecular marker and contribute to the establishment and maintenance of phenotypic characteristics of OCCCas through modulation of EMT/CSC properties.