Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Division of Diagnostic Pathology, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan.
Hum Cell. 2021 Jan;34(1):279-288. doi: 10.1007/s13577-020-00443-6. Epub 2020 Oct 1.
Leiomyosarcoma (LMS) is a rare and aggressive mesenchymal malignancy, derived from smooth muscle cells or precursor mesenchymal stem cells for this tissue type. LMS has highly complex and unstable karyotypes, and the clinical outcomes in patients with LMS remain dismal as evidenced by the 5-year-survival of 64%. Novel therapeutic approaches are required to improve its clinical outcomes. Patient-derived cancer cell lines are indispensable as a tool to study the molecular mechanisms underlying clinical behaviors of tumor cells such as resistance to treatments, metastasis, and recurrence. However, only a limited number of LMS cell lines are publicly available, probably because of the rarity of patients with LMS, and a paucity of cell lines hinders the research on LMS. This study aimed to develop a patient-derived LMS cell line. We successfully established a cell line from the primary tumor tissue of a 90-year-old female patient with pleomorphic LMS, which we named NCC-LMS2-C1. NCC-LMS2-C1 cells were maintained as a monolayer culture for over 29 passages spanning 10 months. NCC-LMS2-C1 cells exhibited continuous growth, the ability to form spheroid, and invasion capability. We screened 213 anti-cancer drugs to find those that have anti-proliferation effects on NCC-LMS2-C1 cells, and identified a histone deacetylase inhibitor, romidepsin. In conclusion, we have established a novel LMS cell line, NCC-LMS2-C1, which will be a useful resource to study the mechanisms of LMS progression and perform high-throughput screening for anti-cancer drug discovery.
平滑肌肉瘤(LMS)是一种罕见且侵袭性的间叶性恶性肿瘤,来源于平滑肌细胞或该组织类型的前体细胞。LMS 具有高度复杂和不稳定的核型,患者的临床结局仍然不佳,5 年生存率为 64%。需要新的治疗方法来改善其临床结局。患者来源的癌细胞系是研究肿瘤细胞如治疗耐药、转移和复发等临床行为的分子机制的不可或缺的工具。然而,只有有限数量的 LMS 细胞系可供公开使用,这可能是因为 LMS 患者罕见,而且细胞系的缺乏阻碍了对 LMS 的研究。本研究旨在建立一个患者来源的 LMS 细胞系。我们成功地从一名 90 岁女性多形性 LMS 原发性肿瘤组织中建立了一个细胞系,我们将其命名为 NCC-LMS2-C1。NCC-LMS2-C1 细胞在超过 10 个月的 29 个传代中以单层培养方式维持。NCC-LMS2-C1 细胞表现出连续生长、形成球体的能力和侵袭能力。我们筛选了 213 种抗癌药物,以寻找对 NCC-LMS2-C1 细胞具有抗增殖作用的药物,并鉴定出组蛋白去乙酰化酶抑制剂罗米地辛。总之,我们建立了一种新型的 LMS 细胞系 NCC-LMS2-C1,它将成为研究 LMS 进展机制和进行高通量筛选抗癌药物发现的有用资源。