Establishment and characterization of NCC-UPS3-C1: a novel patient-derived cell line of undifferentiated pleomorphic sarcoma
Establishment and characterization of NCC-UPS3-C1: a novel patient-derived cell line of undifferentiated pleomorphic sarcoma
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NCC-UPS3-C1 的建立和表征：一种新型的患者来源的未分化多形性肉瘤细胞系
DOI：
10.1007/s13577-021-00633-w
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发表时间：
2021
期刊：
影响因子：
4.3
通讯作者：
Kondo Tadashi
中科院分区：
文献类型：
--
作者：
Tsuchiya Ryuto;Yoshimatsu Yuki;Noguchi Rei;Sin Yooksil;Ono Takuya;Akiyama Taro;Sugaya Jun;Nakatani Fumihiko;Kojima Naoki;Yoshida Akihiko;Ohtori Seiji;Kawai Akira;Kondo Tadashi
未分化多形性肉瘤 (UPS)，以前称为恶性纤维组织细胞瘤，是最具侵袭性的肉瘤之一，没有可识别的分化线。尽管UPS肿瘤发生的分子机制尚未阐明，但辐射暴露被认为是UPS发生的危险因素。在UPS的治疗中，手术治疗仍然是最重要的治疗方式。虽然在不可切除或转移性病例中考虑化疗，但已知 UPS 对常规化疗无效，导致预后不良。为了改善这种情况的临床结果，迫切需要新的治疗方法。患者来源的细胞系是临床前研究的重要工具。然而，由于 UPS 的稀有性，只有四种 UPS 电池系列是公开的。因此，我们利用来自放射相关 UPS 患者的手术切除肿瘤建立了一种新型 UPS 细胞系 NCC-UPS3-C1。 NCC-UPS3-C1 细胞具有多个基因组缺失，包括抑癌基因 CDKN2A 和 CDKN2B。 NCC-UPS3-C1 细胞表现出持续生长、球体形成和侵袭性侵袭能力。我们还使用214种药物进行了筛选试验，发现组蛋白脱乙酰酶抑制剂罗米地辛对NCC-UPS3-C1细胞高度有效。因此，我们得出结论，NCC-UPS3-C1 细胞系是 UPS 临床前研究的有用工具。
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 genesCDKN2AandCDKN2B. 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.