Oyama Rieko, Kito Fusako, Takahashi Mami, Hattori Emi, Noguchi Rei, Takai Yoko, Sakumoto Marimu, Qiao Zhiwei, Toki Shunichi, Sugawara Masato, Tanzawa Yoshikazu, Kobayashi Eisuke, Nakatani Fumihiko, Iwata Shintaro, Yoshida Akihiko, Kawai Akira, Kondo Tadashi
1Department of Innovative Seeds Evaluation, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan.
2Central Animal Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan.
Cancer Cell Int. 2020 Feb 19;20:58. doi: 10.1186/s12935-020-1128-z. eCollection 2020.
Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are dismal, and novel therapeutic strategies are required. Although patient-derived cancer cell lines are vital for basic research and preclinical studies, few MPNST cell lines are available from public cell banks. Therefore, the aim of this study was to establish cancer cell lines derived from MPNST patients.
We used tumor tissues from five patients with MPNSTs, including one derived from a rare bone tissue MPNST. The tumor tissues were obtained at the time of surgery and were immediately processed to establish cell lines. A patient-derived xenograft was also established when a sufficient amount of tumor tissue was available. The characterization of established cells was performed with respect to cell proliferation, spheroid formation, and invasion. The mutation status of actionable genes was monitored by NCC Oncopanel, by which the mutation of 114 genes was assessed by next-generation sequencing. The response to anti-cancer agents, including anti-cancer drugs approved for the treatment of other malignancies was investigated in the established cell lines.
We established five cell lines (NCC-MPNST1-C1, NCC-MPNST2-C1, NCC-MPNST3-C1, NCC-MPNST4-C1, and NCC-MPNST5-C1) from the original tumors, and also established patient-derived xenografts (PDXs) from which one cell line (NCC-MPNST3-X2-C1) was produced. The established MPNST cell lines proliferated continuously and formed spheroids while exhibiting distinct invasion abilities. The cell lines had typical mutations in the actionable genes, and the mutation profiles differed among the cell lines. The responsiveness to examined anti-cancer agents differed among cell lines; while the presence of an actionable gene mutation did not correspond with the response to the anticipated anti-cancer agents.
The established cell lines exhibit various characteristics, including proliferation and invasion potential. In addition, they had different mutation profiles and response to the anti-cancer agents. These observations suggest that the established cell lines will be useful for future research on MPNSTs.
恶性外周神经鞘瘤（MPNSTs）是软组织肉瘤的一种罕见亚型，起源于外周分支或坐骨神经、臂丛神经或骶丛神经的神经鞘。对于无法切除或转移性肿瘤的MPNST患者，临床预后不佳，需要新的治疗策略。虽然患者来源的癌细胞系对基础研究和临床前研究至关重要，但公共细胞库中可用的MPNST细胞系很少。因此，本研究的目的是建立源自MPNST患者的癌细胞系。
我们使用了5例MPNST患者的肿瘤组织，其中1例源自罕见的骨组织MPNST。肿瘤组织在手术时获取，并立即进行处理以建立细胞系。当有足够量的肿瘤组织时，还建立了患者来源的异种移植模型。对建立的细胞进行细胞增殖、球体形成和侵袭方面的表征。通过NCC Oncopanel监测可操作基因的突变状态，通过下一代测序评估114个基因的突变情况。在建立的细胞系中研究了对包括已批准用于治疗其他恶性肿瘤的抗癌药物在内的抗癌药物的反应。
我们从原始肿瘤中建立了5个细胞系（NCC-MPNST1-C1、NCC-MPNST2-C1、NCC-MPNST3-C1、NCC-MPNST4-C1和NCC-MPNST5-C1），还建立了患者来源的异种移植模型（PDXs），从中产生了1个细胞系（NCC-MPNST3-X2-C1）。建立的MPNST细胞系持续增殖并形成球体，同时表现出不同的侵袭能力。这些细胞系在可操作基因中具有典型突变，且细胞系之间的突变谱不同。细胞系对所检测的抗癌药物的反应不同；虽然可操作基因突变的存在与对预期抗癌药物的反应不相关。
建立的细胞系表现出各种特性，包括增殖和侵袭潜能。此外，它们具有不同的突变谱和对抗癌药物的反应。这些观察结果表明，建立的细胞系将有助于未来MPNSTs的研究。
