Wang Feng, Zhang Zhiyu, Li Qin, Yu Tao, Ma Chengbin
Department of Orthopedics, the Fourth Affiliated Hospital of China Medical University, Chongshan Road, Shenyang, 110032 Liaoning People's Republic of China.
Center for Translational Medicine, the Fourth Affiliated Hospital of China Medical University, Chongshan Road, Shenyang, 110032 Liaoning People's Republic of China.
Cancer Cell Int. 2020 Jun 24;20:269. doi: 10.1186/s12935-020-01356-y. eCollection 2020.
Cancer stem cell (CSC) is identified in osteosarcoma (OS) and considered resistant to chemotherapeutic agents. However, the mechanism of osteosarcoma stem cell (OSC) resistant to chemotherapy remains debatable and vague, and the metabolomics feature of OSC is not clarified.
OSC was isolated by using sphere forming assay and identified. Untargeted LC-MS/MS analysis was performed to reveal the metabolomics feature of OSC and underlying mechanisms of OSC resistant to methotrexate (MTX).
OSC was efficiently isolated and identified from human OS 143B and MG63 cell lines with enhanced chemo-resistance to MTX. The untargeted LC-MS analysis revealed that OSC showed differential metabolites and perturbed signaling pathways, mainly involved in metabolisms of fatty acid, amino acid, carbohydrate metabolism and nucleic acid. After treated with MTX, metabolomics feature of OSC was mainly involved metabolisms of amino acid, fatty acid, energy and nucleic acid. Moreover, compared with their parental OS cells response to MTX, the differential metabolites and perturbed signaling pathways were mainly involved in metabolism of amino acid, fatty acid and nucleic acid. What's more, Rap1 signaling pathway and Ras signaling pathway were involved in OS cells and their SCs response to MTX.
Sphere-forming assay was able to efficiently isolate OSC from human OS cell lines and the untargeted LC-MS/MS analysis was suggested a sufficient methodology to investigate metabolomics features of OS cells and OSCs. Moreover, the metabolomics features of OSCs response to MTX might reveal a further understanding of chemotherapeutic resistance in OS.
癌症干细胞（CSC）在骨肉瘤（OS）中被鉴定出来，并被认为对化疗药物具有抗性。然而，骨肉瘤干细胞（OSC）对化疗产生抗性的机制仍存在争议且尚不明确，并且OSC的代谢组学特征也未得到阐明。
通过球体形成实验分离并鉴定OSC。进行非靶向液相色谱-质谱/质谱分析以揭示OSC的代谢组学特征以及OSC对甲氨蝶呤（MTX）产生抗性的潜在机制。
从人OS 143B和MG63细胞系中高效分离并鉴定出OSC，其对MTX的化疗抗性增强。非靶向液相色谱分析显示，OSC表现出不同的代谢物和受干扰的信号通路，主要涉及脂肪酸、氨基酸、碳水化合物代谢和核酸代谢。用MTX处理后，OSC的代谢组学特征主要涉及氨基酸、脂肪酸、能量和核酸代谢。此外，与它们的亲代OS细胞对MTX的反应相比，差异代谢物和受干扰的信号通路主要涉及氨基酸、脂肪酸和核酸代谢。更重要的是，Rap1信号通路和Ras信号通路参与了OS细胞及其干细胞对MTX的反应。
球体形成实验能够从人OS细胞系中高效分离出OSC，并且非靶向液相色谱-质谱/质谱分析被认为是研究OS细胞和OSC代谢组学特征的充分方法。此外，OSC对MTX反应的代谢组学特征可能有助于进一步了解OS中的化疗抗性。
