Sphere-forming cells display stem cell-like characteristics and increased xCT expression in a canine hepatocellular carcinoma cell line
Sphere-forming cells display stem cell-like characteristics and increased xCT expression in a canine hepatocellular carcinoma cell line
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DOI：
10.1016/j.rvsc.2021.06.013
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发表时间：
2021-07-08
影响因子：
2.4
通讯作者：
Itamoto, Kazuhito
中科院分区：
文献类型：
--
作者：
Itoh, Harumichi;Tani, Kenji;Itamoto, Kazuhito
肝细胞癌是犬原发性肝肿瘤中最常见的一种，然而，由于抗癌药物的耐药性，大多数针对肝细胞癌的化疗都是无效的。球体形成细胞被认为是各种实体瘤的肿瘤干细胞，并已在许多犬肿瘤细胞系中建立，但尚未有关于犬肝细胞癌球体形成细胞的研究报道。在本研究中，我们从犬肝癌细胞系(AZACH)中建立了球状细胞。这些细胞表现出干细胞标志物(Nanog、Sox2、c-Myc和KLF4)表达增加，乙醛脱氢酶活性增强，对米托蒽醌、吉西他滨和阿霉素耐药。此外，与贴壁细胞相比，球形细胞表现出更高的XCT表达和更低的细胞内活性氧水平。用一种XCT特异性抑制剂柳氮磺吡啶治疗，会降低球体形成效率。综上所述，这些结果表明，来自犬肝癌细胞系的球体形成细胞具有与癌症干细胞相似的特征，它们XCT表达的增加和相关的对氧化应激的抵抗有助于球体的形成。
Hepatocellular carcinoma (HCC) is the most common type of canine primary liver tumor; however, most chemotherapies against HCC are ineffective due to resistance to anticancer agents. Sphere-forming cells are considered to act as cancer stem cells for various types of solid tumors and have been established for many canine tumor cell lines, yet no studies have reported sphere-forming cells for canine HCC. In this study, we established sphere-forming cells from a canine HCC cell line (AZACH). These cells displayed increased stem cell marker mRNA expression (Nanog, Sox2, c-Myc, and Klf4), aldehyde dehydrogenase activity, and chemoresistance against mitoxantrone, gemcitabine, and doxorubicin. In addition, sphere-forming cells exhibited higher xCT expression and lower intracellular reactive oxygen species levels than adherent cells. Treatment with sulfasalazine, a xCT-specific inhibitor, reduced sphere formation efficiency. Together, these results indicate that sphere forming cells derived from a canine HCC cell line have similar characteristics to cancer stem cells and that their increased xCT expression and associated resistance to oxidative stress contribute toward sphere formation.