当前位置: X-MOL 学术Cancer Cell Int. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors.
Cancer Cell International ( IF 5.8 ) Pub Date : 2020-02-19 , DOI: 10.1186/s12935-020-1128-z
Rieko Oyama 1 , Fusako Kito 1 , Mami Takahashi 2 , Emi Hattori 3 , Rei Noguchi 3 , Yoko Takai 1 , Marimu Sakumoto 1 , Zhiwei Qiao 3 , Shunichi Toki 4 , Masato Sugawara 4 , Yoshikazu Tanzawa 4 , Eisuke Kobayashi 4 , Fumihiko Nakatani 4 , Shintaro Iwata 4 , Akihiko Yoshida 5 , Akira Kawai 4 , Tadashi Kondo 1, 3
Affiliation  

Background 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. Methods 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. Results 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. Conclusion 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.

中文翻译:

恶性周围神经鞘瘤患者源性癌症模型的建立和表征。

背景恶性外周神经鞘瘤(MPNSTs)是一种罕见的软组织肉瘤亚型,来源于坐骨神经、臂丛或骶丛的外周分支或鞘。患有不可切除或转移性肿瘤的 MPNST 患者的临床结果令人沮丧,需要新的治疗策略。尽管源自患者的癌细胞系对于基础研究和临床前研究至关重要,但很少有 MPNST 细胞系可从公共细胞库获得。因此,本研究的目的是建立源自 MPNST 患者的癌细胞系。方法 我们使用了来自 5 名 MPNST 患者的肿瘤组织,其中一名来自罕见的骨组织 MPNST。在手术时获得肿瘤组织并立即处理以建立细胞系。当有足够数量的肿瘤组织可用时,还建立了源自患者的异种移植物。在细胞增殖、球体形成和侵袭方面对已建立的细胞进行了表征。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。在已建立的细胞系中研究了对抗癌药物的反应,包括批准用于治疗其他恶性肿瘤的抗癌药物。结果我们从原始肿瘤中建立了五个细胞系(NCC-MPNST1-C1、NCC-MPNST2-C1、NCC-MPNST3-C1、NCC-MPNST4-C1和NCC-MPNST5-C1),并建立了患者来源的异种移植物(PDX),从中产生一个细胞系 (NCC-MPNST3-X2-C1)。已建立的 MPNST 细胞系不断增殖并形成球体,同时表现出明显的入侵能力。细胞系在可操作基因中具有典型的突变,并且细胞系之间的突变谱不同。不同细胞系对检测到的抗癌剂的反应不同;而可操作基因突变的存在与对预期抗癌剂的反应不相符。结论 建立的细胞系表现出多种特征,包括增殖和侵袭潜力。此外,它们具有不同的突变谱和对抗癌剂的反应。这些观察结果表明,已建立的细胞系将对未来的 MPNST 研究有用。细胞系在可操作基因中具有典型的突变,并且细胞系之间的突变谱不同。不同细胞系对检测到的抗癌剂的反应不同;而可操作基因突变的存在与对预期抗癌剂的反应不相符。结论 建立的细胞系表现出多种特征,包括增殖和侵袭潜力。此外,它们具有不同的突变谱和对抗癌剂的反应。这些观察结果表明,已建立的细胞系将对未来的 MPNST 研究有用。细胞系在可操作基因中具有典型的突变,并且细胞系之间的突变谱不同。不同细胞系对检测到的抗癌剂的反应不同;而可操作基因突变的存在与对预期抗癌剂的反应不相符。结论 建立的细胞系表现出多种特征,包括增殖和侵袭潜力。此外,它们具有不同的突变谱和对抗癌剂的反应。这些观察结果表明,已建立的细胞系将对未来的 MPNST 研究有用。而可操作基因突变的存在与对预期抗癌剂的反应不相符。结论 建立的细胞系表现出多种特征,包括增殖和侵袭潜力。此外,它们具有不同的突变谱和对抗癌剂的反应。这些观察结果表明,已建立的细胞系将对未来的 MPNST 研究有用。而可操作基因突变的存在与对预期抗癌剂的反应不相符。结论 建立的细胞系表现出多种特征,包括增殖和侵袭潜力。此外,它们具有不同的突变谱和对抗癌剂的反应。这些观察结果表明,已建立的细胞系将对未来的 MPNST 研究有用。
更新日期:2020-02-19
down
wechat
bug