New therapeutic strategy using specific fusion genes of bone and soft-tissue sarcomas

1. 我们制备了两种针对SYT-SSX2蛋白n端和c端部分的多克隆抗体。这些抗体还可以用免疫沉淀法在人滑膜肉瘤细胞株（HS-SY41）的裂解液中检测到60 kDa的天然蛋白，用western blot分析在人滑膜肉瘤的提取物中检测到60 kDa的天然蛋白2。在人滑膜肉瘤a3中，SYT-SSX融合基因产物分子量为60 kDa。SYT-SSX2转染后，NIH3T3细胞形态发生改变，集落形成活性增强。转染SYT-SSX1和2的NIH3T3细胞接种裸鼠后，均在裸鼠体内产生肿瘤4。我们开发了SYT-SSX融合基因的反义寡核苷酸，它能抑制滑膜肉瘤细胞的增殖，但对纤维肉瘤细胞没有抑制作用5。在一例22岁的滑膜肉瘤孕妇中，采用巢式聚合酶链反应（PCR）在活检前采集的外周血中检测到SYT-SSX融合基因转录物。化疗后和两例骨肉瘤患者外周血中均未检测到SYT-SSX融合基因转录物。这些发现提示循环肿瘤细胞应该被监测，因为它们可以作为滑膜肉瘤的预后指标

1. We developed two polyclonal antibodies against the N-terminal part and for the C-terminal part of the SYT-SSX2 protein. These antibodies also detected the native protein of 60 kDa in the lysate of a human synovial sarcoma cell line (HS-SY41) with immunoprecipitation, and in extracts of human synovial sarcomas with western blot analysis2. The molecular weight of the SYT-SSX fusion gene product was 60 kDa in human synovial sarcoma3. The NIH3T3 cells transfected with SYT-SSX2 showed a morphological change and colony-forming activity. Both NIH3T3 cells transfected with SYT-SSX1 and 2 produced tumors in nude mice, when the 5xl0^5 cells were inoculated into nude mice4. We developed the antisense oligo DNAs against SYT-SSX fusion gene, which inhibited proliferation of synovial sarcoma cells, but not fibrosarcoma cells5. In a 22-year-old pregnant woman with synovial sarcoma, the SYT-SSX fusion gene transcript was detected by nested polymerase chain reaction (PCR) in the peripheral blood collected before biopsy. The SYT-SSX fusion gene transcript was not detected after chemotherapy and from the peripheral blood from two osteosarcoma patients. These findings suggest that circulating tumor cells should be monitored because they may serve as a prognostic indicator for synovial sarcoma