Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li?Fraumeni syndrome
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li?Fraumeni syndrome
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NCC-UPS4-C1 的建立和表征：来自 Li?Fraumeni 综合征患者的未分化多形性肉瘤的新型细胞系
DOI：
10.1007/s13577-022-00671-y
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发表时间：
2022
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：
Ono Takuya;Yoshimatsu Yuki;Noguchi Rei;Sin Yooksil;Tsuchiya Ryuto;Akiyama Taro;Sugaya Jun;Fukushima Suguru;Kojima Naoki;Yoshida Akihiko;Kawai Akira;Kondo Tadashi
Li-Fraumeni综合征（LFS）是一种由TP 53基因突变引起的癌症易感综合征。LFS患者的终生癌症风险男性≥ 70%，女性≥ 90%。未分化多形性肉瘤（UPS）是与LFS相关的核心癌症之一。UPS是未分化软组织肉瘤的一个亚型，没有可识别的分化线。UPS的标准治疗方法是完全手术切除。然而，局部复发和远处转移到肺，通常可以发现切除后的UPS。因此，需要一种新的UPS患者治疗策略。虽然特征很好，但患者来源的肿瘤细胞系有助于大量药物的高通量筛选，并且没有来自LFS患者的肉瘤细胞系在公共细胞库中注册。因此，本研究旨在从LFS患者中建立一种新的，充分表征的UPS细胞系。从手术切除的UPS肿瘤组织中，我们建立了来自LFS患者的第一个UPS细胞系，并将其命名为NCC-UPS 4-C1。NCC-UPS 4-C1存在拷贝数改变和TP 53抑癌基因突变。细胞具有恒定的细胞生长和侵袭能力。然后，利用这种充分表征的NCC-UPS 4-C1细胞系对214种抗癌药物进行高通量筛选，并鉴定出两种有效药物。这两种药物之一，罗米地辛，通常是有效的NCC-UPS 1-C1，NCC-UPS 2-C1，和NCC-UPS 3-C1细胞系，我们以前报告;一个潜在的药物治疗UPS建议使用良好的UPS细胞系。这些数据表明，NCC-UPS 4-C1是从LFS患者中建立的第一个肉瘤细胞系，使研究人员能够对UPS进行积极的临床前研究。
Li–Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by a germline mutation of theTP53. The lifetime risk of cancer in individuals with LFS is ≥ 70% for men and ≥ 90% for women. Undifferentiated pleomorphic sarcoma (UPS) is one of the core cancers associated with LFS. UPS is a subtype of undifferentiated soft tissue sarcoma that shows no identifiable line of differentiation. The standard curative treatment for UPS is complete surgical resection. However, local recurrence and distant metastasis to the lung can usually be found after resection of the UPS. Therefore, a novel treatment strategy for patients with UPS is required. Although well characterized, patient-derived tumor cell lines facilitate the high-throughput screening of a large number of drugs, and no sarcoma cell lines derived from a patient with LFS have been registered in public cell banks. Thus, this study aimed to establish a novel, well-characterized UPS cell line from a patient with LFS. From surgically resected UPS tumor tissues, we established the first UPS cell line from a patient with LFS and named it NCC-UPS4-C1. NCC-UPS4-C1 harbored copy number alterations and had theTP53tumor suppressor gene mutation. The cells exhibited constant cell growth and invasive ability. This well-characterized NCC-UPS4-C1 cell line was then utilized for high-throughput screening of 214 anti-cancer drugs, and two effective drugs were identified. One of the two drugs, romidepsin, was commonly effective for the NCC-UPS1-C1, NCC-UPS2-C1, and NCC-UPS3-C1 cell lines that we previously reported; a potential drug for the treatment of UPS was suggested using well-characterized UPS cell lines. These data indicate that NCC-UPS4-C1, which is the first sarcoma cell line established from a patient with LFS, enables researchers to conduct vigorous preclinical research on UPS.