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建立并鉴定 NCC-GCTB14-C1 和 NCC-GCTB15-C1:两种新型的骨巨细胞瘤患者来源细胞系。

Establishment and characterization of NCC-GCTB14-C1 and NCC-GCTB15-C1: two novel patient-derived cell lines of giant cell tumor of bone.

机构信息

Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8670, Japan.

出版信息

Hum Cell. 2024 Nov 27;38(1):20. doi: 10.1007/s13577-024-01150-2.

Abstract

Giant cell tumor of bone (GCTB) is a rare bone tumor that is genetically characterized by a unique mutation in the H3-3A gene. Curative surgical resection is the standard treatment. Unfortunately, a considerable proportion of patients with GCTB have local recurrence and pulmonary metastasis after surgical treatment, and current chemotherapy treatments have shown non-effective. Considering the heterogeneity of the disease, patient-derived cancer models established from multiple cases are required. Therefore, we aimed to establish novel GCTB cell lines for use in preclinical studies. In this study, we successfully established two GCTB cell lines, NCC-GCTB14-C1 and NCC-GCTB15-C1. Both cell lines retained the genetic characteristics of the original tumors, constantly proliferated, and exhibited migratory activity. These cells formed spheroids with morphologically variable phenotypes. We found that they were compatible with chemosensitivity assays, and drug screening using these cell lines led to the identification of potential therapeutic candidates for GCTB. Therefore, NCC-GCTB14-C1 and NCC-GCTB15-C1 may be useful for elucidating the pathogenesis of and developing novel treatments for GCTB.

摘要

骨巨细胞瘤(GCTB)是一种罕见的骨肿瘤,其遗传特征是 H3-3A 基因的独特突变。根治性手术切除是标准治疗方法。不幸的是,相当一部分 GCTB 患者在手术后会出现局部复发和肺转移,目前的化疗治疗效果不佳。考虑到疾病的异质性,需要建立多个病例来源的患者源性癌症模型。因此,我们旨在建立新的 GCTB 细胞系,用于临床前研究。在这项研究中,我们成功建立了两个 GCTB 细胞系,NCC-GCTB14-C1 和 NCC-GCTB15-C1。这两个细胞系保留了原始肿瘤的遗传特征,持续增殖,并表现出迁移活性。这些细胞形成具有形态学可变表型的球体。我们发现它们与化疗敏感性测定相容,并且使用这些细胞系进行药物筛选导致鉴定出 GCTB 的潜在治疗候选物。因此,NCC-GCTB14-C1 和 NCC-GCTB15-C1 可能有助于阐明 GCTB 的发病机制并开发新的治疗方法。

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