Hum Cell. 2021 Oct 19.
Ryuto Tsuchiya,
Yuki Yoshimatsu,
Rei Noguchi,
Yooksil Sin,
Takuya Ono,
Taro Akiyama,
Jun Sugaya,
Fumihiko Nakatani,
Naoki Kojima,
Akihiko Yoshida,
Seiji Ohtori,
Akira Kawai,
Tadashi Kondo.
Undifferentiated pleomorphic sarcoma (UPS), previously termed malignant fibrous histiocytoma, is one of the most aggressive sarcomas with no identifiable line of differentiation. Although the molecular mechanism of oncogenesis in UPS has not been clarified, radiation exposure is considered to be a risk factor in the development of UPS. In the treatment of UPS, surgical treatment remains the most important modality. While chemotherapy is considered in unresectable or metastatic cases, UPS is known to be refractory to conventional chemotherapy, leading to an unfavorable prognosis. To improve the clinical outcome of this condition, novel treatment methods are urgently needed. Patient-derived cell lines are essential tools in preclinical studies. However, owing to the rarity of UPS, only four UPS cell lines are publicly available. Thus, we established a novel UPS cell line, NCC-UPS3-C1, using a surgically resected tumor from a patient with radiation-associated UPS. NCC-UPS3-C1 cells had multiple genomic deletions including the tumor suppressor genes CDKN2A and CDKN2B. NCC-UPS3-C1 cells demonstrated constant growth, spheroid formation, and aggressive invasion ability. We also conducted a screening test using 214 drugs and identified that the histone deacetylase inhibitor, romidepsin, is highly effective on NCC-UPS3-C1 cells. Thus, we concluded that the NCC-UPS3-C1 cell line is a useful tool in preclinical studies for UPS.
Keywords: Drug screening; Patient-derived cell line; Radiation-associated sarcoma; Sarcoma; Undifferentiated pleomorphic sarcoma