Noguchi Rei, Ono Takuya, Osaki Julia, Adachi Yuki, Iwata Shuhei, Shiota Yomogi, Yanagihara Kazuyoshi, Nishino Shogo, Funada Takaya, Ogura Koichi, Yoshida Akihiko, 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 Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Hum Cell. 2024 Dec 8;38(1):28. doi: 10.1007/s13577-024-01152-0.
Chondrosarcoma (CS) is a malignant tumor that produces cartilaginous matrix and is the second most common primary bone sarcoma. CS encompasses a range of histological subtypes, with high-grade conventional central CS being particularly rare, occurring at a rate of 1.81 cases per 1 million person-years. Complete surgical resection is the standard curative treatment for this subtype, as radiation therapy and chemotherapy have proven ineffective. High-grade conventional central CS is highly metastatic and prone to recurrence, resulting in a poor prognosis. Therefore, effective multidisciplinary treatment strategies are urgently needed. Patient-derived cell lines offer promising tools for exploring new therapeutic approaches. However, only two cell lines of high-grade CSs are currently available in public cell banks. In this study, we aimed to establish a novel cell line for high-grade conventional central CS. We successfully developed the NCC-CS1-C1 cell line using surgically resected tumor tissues from a patient with conventional central grade 3 CS. This cell line harbored an IDH1 mutation (p.R132S), commonly found in 50% of CS cases, and exhibited complex copy number variants. A high-throughput screening of 221 anti-cancer drugs identified five candidates-bortezomib, carfilzomib, doxorubicin, panobinostat, and romidepsin-that demonstrated low IC50 values, indicating potential efficacy in treating CS. These findings suggest that NCC-CS1-C1 is a valuable tool for both preclinical and basic research on high-grade conventional central CS.
软骨肉瘤(CS)是一种产生软骨基质的恶性肿瘤,是第二常见的原发性骨肉瘤。CS包括一系列组织学亚型,高级别传统中央型CS尤为罕见,发病率为每100万人年1.81例。完全手术切除是该亚型的标准治愈性治疗方法,因为放疗和化疗已被证明无效。高级别传统中央型CS具有高度转移性且易于复发,导致预后不良。因此,迫切需要有效的多学科治疗策略。患者来源的细胞系为探索新的治疗方法提供了有前景的工具。然而,目前公共细胞库中仅有两种高级别CS细胞系。在本研究中,我们旨在建立一种用于高级别传统中央型CS的新型细胞系。我们使用一名患有传统中央型3级CS患者的手术切除肿瘤组织成功开发了NCC-CS1-C1细胞系。该细胞系存在IDH1突变(p.R132S),常见于50%的CS病例中,并表现出复杂的拷贝数变异。对221种抗癌药物的高通量筛选确定了五种候选药物——硼替佐米、卡非佐米、阿霉素、帕比司他和罗米地辛——它们的半数抑制浓度(IC50)值较低,表明在治疗CS方面具有潜在疗效。这些发现表明,NCC-CS1-C1对于高级别传统中央型CS的临床前和基础研究都是一种有价值的工具。