Akiyama Taro, Yoshimatsu Yuki, Noguchi Rei, Sin Yooksil, Osaki Julia, Ono Takuya, Adachi Yuki, Tsuchiya Ryuto, Toda Yu, Ogura Koichi, Kojima Naoki, Yoshida Akihiko, Ohtori Seiji, Kawai Akira, Kondo Tadashi
Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-Shi, Chiba, 260-8670, Japan.
Hum Cell. 2023 Nov;36(6):2187-2194. doi: 10.1007/s13577-023-00932-4. Epub 2023 Jul 25.
Dermatofibrosarcoma protuberans (DFSP) is a superficial low-grade sarcoma, genetically characterized by a fusion gene in collagen type I α (COL1A1) gene and platelet-derived growth factor subunit β (PDGFB). DFSP is locally aggressive and does not typically metastasize. However, DFSP with fibrosarcomatous transformation, which occurs in 7-16% of DFSP cases, demonstrates a poor prognosis than classic DFSP with a higher local recurrence rate and metastatic potential. Although imatinib, a PDGF receptor inhibitor, is a potent therapeutic agent for classic DFSP, it is less effective for DFSP with fibrosarcomatous transformation. The development of definitive chemotherapies for DFSP with fibrosarcomatous transformation is required. Patient-derived tumor cell lines are indispensable tools for preclinical research to discover novel therapeutic agents. However, only seven cell lines were derived from DFSP, out of which only two were established from DFSP with fibrosarcomatous transformation. Hence, in the present study, we established a novel DFSP cell line, NCC-DFSP4-C1, from a surgically resected DFSP tumor specimen with fibrosarcomatous transformation. NCC-DFSP4-C1 harbored an identical COL1A1-PDGFB fusion gene as its donor tumor. NCC-DFSP4-C1 cells retained the morphology of their donor tumor and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. By screening a drug library, we found that bortezomib and romidepsin demonstrated the strongest suppressive effects on the proliferation of NCC-DFSP4-C1 cells. In conclusion, we report a novel cell line of DFSP with fibrosarcomatous transformation, and demonstrate its utility in the development of novel therapeutic agents for DFSP.
隆突性皮肤纤维肉瘤（DFSP）是一种浅表性低级别肉瘤，其基因特征为I型胶原蛋白α（COL1A1）基因与血小板衍生生长因子β亚基（PDGFB）的融合基因。DFSP具有局部侵袭性，通常不发生转移。然而，发生在7%-16%的DFSP病例中的伴有纤维肉瘤样转化的DFSP，其预后比经典DFSP差，局部复发率和转移潜能更高。尽管伊马替尼（一种PDGF受体抑制剂）是经典DFSP的有效治疗药物，但对伴有纤维肉瘤样转化的DFSP效果较差。因此需要开发针对伴有纤维肉瘤样转化的DFSP的确定性化疗方法。患者来源的肿瘤细胞系是发现新型治疗药物的临床前研究不可或缺的工具。然而，仅从DFSP中获得了7个细胞系，其中只有2个是从伴有纤维肉瘤样转化的DFSP中建立的。因此，在本研究中，我们从一个手术切除的伴有纤维肉瘤样转化的DFSP肿瘤标本中建立了一个新的DFSP细胞系NCC-DFSP4-C1。NCC-DFSP4-C1含有与其供体肿瘤相同的COL1A1-PDGFB融合基因。NCC-DFSP4-C1细胞保留了其供体肿瘤的形态，并在体外表现出持续增殖、球体形成和侵袭能力。通过筛选药物库，我们发现硼替佐米和罗米地辛对NCC-DFSP4-C1细胞的增殖具有最强的抑制作用。总之，我们报告了一种新的伴有纤维肉瘤样转化的DFSP细胞系，并证明了其在开发DFSP新型治疗药物中的应用价值。
