Adachi Yuki, Noguchi Rei, Osaki Julia, Ono Takuya, Akiyama Taro, Kondo Hiroya, Kobayashi Eisuke, Kojima Naoki, Yoshida Akihiko, Yokoo Hideki, Kawai Akira, Kondo Tadashi
Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido, Japan.
Hum Cell. 2024 Dec 9;38(1):29. doi: 10.1007/s13577-024-01153-z.
Giant cell tumor of bone (GCTB) is a rare osteolytic tumor composed of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. While generally benign, GCTB has a high risk of local recurrence and can occasionally undergo malignant transformation or metastasis, posing significant clinical challenges. The primary treatment is complete surgical resection; however, effective management strategies for recurrent or advanced GCTB remain elusive, underscoring the need for further preclinical research. This study reports the establishment of a novel cell line, NCC-GCTB10-C1, derived from a recurrent GCTB lesion. NCC-GCTB10-C1 retains the characteristic H3-3A G34W mutation, which is central to the tumor's pathogenesis, and demonstrates significant growth potential, spheroid formation capability, and invasive properties. Extensive drug screening of NCC-GCTB10-C1, along with nine previously established GCTB cell lines, revealed a distinct drug response profile, with the cell line showing resistance to many previously effective agents. However, doxorubicin, foretinib, and ceritinib were identified as promising therapeutic candidates due to their low IC values in NCC-GCTB10-C1. The establishment of NCC-GCTB10-C1 offers a critical resource for further research into GCTB, especially in the context of recurrent disease, and holds potential for the development of more effective treatment strategies.
骨巨细胞瘤(GCTB)是一种罕见的溶骨性肿瘤,由单核基质细胞、巨噬细胞和破骨细胞样巨细胞组成。虽然GCTB通常为良性,但具有较高的局部复发风险,偶尔会发生恶性转化或转移,带来重大临床挑战。主要治疗方法是完整手术切除;然而,对于复发性或晚期GCTB的有效管理策略仍不明确,这凸显了进一步开展临床前研究的必要性。本研究报告了一种源自复发性GCTB病变的新型细胞系NCC - GCTB10 - C1的建立。NCC - GCTB10 - C1保留了特征性的H3 - 3A G34W突变,该突变是肿瘤发病机制的核心,并表现出显著的生长潜力、球体形成能力和侵袭特性。对NCC - GCTB10 - C1以及九个先前建立的GCTB细胞系进行广泛的药物筛选,发现了独特的药物反应谱,该细胞系对许多先前有效的药物具有抗性。然而,由于阿霉素、foretinib和色瑞替尼在NCC - GCTB10 - C1中的低IC值,它们被确定为有前景的治疗候选药物。NCC - GCTB10 - C1的建立为进一步研究GCTB,特别是在复发性疾病背景下,提供了关键资源,并为开发更有效的治疗策略带来了潜力。