The properties of tumor-initiating cells from a hepatocellular carcinoma patient's primary and recurrent tumor
The properties of tumor-initiating cells from a hepatocellular carcinoma patient's primary and recurrent tumor
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肝细胞癌患者原发性和复发性肿瘤的肿瘤起始细胞的特性
DOI：
10.1093/carcin/bgp232
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发表时间：
2010-02-01
期刊：
影响因子：
4.7
通讯作者：
Zhang, Zhi-Qian
中科院分区：
文献类型：
--
作者：
Xu, Xiao-Lan;Xing, Bao-Cai;Zhang, Zhi-Qian
肝细胞癌（HCC）由于其高复发率而与高发病率和死亡率相关。然而，很少有人知道复发性肝癌细胞的生物学特性。通过原代培养分别建立单个患者的原发性和复发性HCC衍生的细胞系Hep-11和Hep-12。这两个细胞系具有相同的B型肝炎病毒整合位点，并共享许多共同的扩增和缺失，这表明它们具有相同的克隆起源。虽然Hep-11细胞在注射多达10 000个细胞后16周时无致瘤性，但仅注射100个Hep-12细胞就足以引发肿瘤生长，并且所有单个Hep-12克隆在免疫缺陷小鼠中均具有致瘤性。与Hep-11相比，Hep-12细胞表达卵圆细胞标志物AFP、NCAM/CD 56、c-kit/CD 117，以及多个干细胞标志物Nanog、OCT 4和SOX 2。此外，> 90%的Hep-12细胞为乙醛脱氢酶阳性。他们对紫杉醇的耐药性也较低，但对阿霉素、顺铂和羟基喜树碱（HCPT）的耐药性更高。此外，Hep-12细胞比Hep-11表达更高水平的聚（腺苷二磷酸-核糖）聚合酶-1（PARP-1），并且PARP-1抑制增强Hep-12细胞对HCPT的敏感性，但Hep-11细胞中没有。这些结果表明，大量复发的HCC衍生的Hep-12细胞是肿瘤起始细胞，并且PARP-1的表达升高与它们对HCPT的抗性有关。
Hepatocellular carcinoma (HCC) is associated with a high morbidity and mortality due to its high rate of recurrence. However, little is known about the biological characteristics of recurrent HCC cells. A single patient's primary and recurrent HCC-derived cell lines, Hep-11 and Hep-12, respectively, were established by primary culture. These two cell lines have the same hepatitis B virus integration site and share many common amplifications and deletions, which suggest that they have the same clonal origin. While Hep-11 cells were non-tumorigenic at 16 weeks following injection of up to 10 000 cells, injection of only 100 Hep-12 cells was sufficient to initiate tumor growth, and all single Hep-12 clones were tumorigenic in immunodeficient mice. Compared with Hep-11, Hep-12 cells expressed the oval cell markers AFP, NCAM/CD56, c-kit/CD117, as well as multiple stem cell markers such as Nanog, OCT4 and SOX2. In addition, > 90% of Hep-12 cells were aldehyde dehydrogenase positive. They were also less resistant to paclitaxel, but more resistant to doxorubicin, cisplatin and hydroxycamptothecin (HCPT), which had been administrated to the patient. Furthermore, Hep-12 cells expressed higher levels of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) than Hep-11, and PARP-1 inhibition potentiated the sensitivity to HCPT in Hep-12 cells but not in Hep-11 cells. These results indicate that a large population of the recurrent HCC-derived Hep-12 cells were tumor-initiating cells and that elevated expression of PARP-1 was related to their resistance to HCPT.