Pathology Department, Tianjin First Center Hospital, Tianjin 300192, P.R. China.
Biological Sample Resource Sharing Center, Tianjin First Center Hospital, Tianjin 300192, P.R. China.
Mol Med Rep. 2019 Jun;19(6):4623-4630. doi: 10.3892/mmr.2019.10160. Epub 2019 Apr 12.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide, which is partially due to the lack of appropriate therapeutic options. The development of HCC is accompanied with unique and continuous genomic and epigenetic modifications. Therefore, the absence of a personalized and reproducible human model reduces the ability to determine the potential of candidate treatments. Conditional reprogramming (CR) culture has been used to establish and indefinitely grow patient‑derived tumor cell lines in a rapid and efficient manner. In the present study, primary HCC cells were isolated from tumor specimens and cultured under CR conditions. The proliferative potential and capacity of cells to undergo continuous regeneration were evaluated by cell viability and proliferation assays, and the expression of tumor‑specific markers was determined by western blotting and immunofluorescence to determine the prospects for use in clinical settings. It was demonstrated that ~55% of tumor samples were able to generate HCC cells that could be continuously expanded and passaged under CR conditions; this ability was associated with the source and composition of the tumor tissues. Furthermore, the expression of the tumor‑specific marker α‑fetoprotein and the proliferative ability of cells were maintained following cycles of cryopreservation and resuscitation. In conclusion, with further optimization, the CR system may be a useful tool for the precise therapeutic treatment of patients with HCC.
肝细胞癌 (HCC) 是全球癌症死亡的第三大主要原因,部分原因是缺乏适当的治疗选择。HCC 的发生伴随着独特且持续的基因组和表观遗传改变。因此,缺乏个性化和可重复的人类模型降低了确定候选治疗方法潜力的能力。条件重编程 (CR) 培养已被用于快速有效地建立和无限期生长患者来源的肿瘤细胞系。在本研究中,从肿瘤标本中分离出原代 HCC 细胞,并在 CR 条件下培养。通过细胞活力和增殖测定评估细胞的增殖潜力和连续再生能力,并通过 Western blot 和免疫荧光测定确定肿瘤特异性标志物的表达,以确定在临床环境中的应用前景。结果表明,约 55%的肿瘤样本能够生成可在 CR 条件下连续扩增和传代的 HCC 细胞;这种能力与肿瘤组织的来源和组成有关。此外,在冷冻保存和复苏循环后,肿瘤特异性标志物α-胎蛋白的表达和细胞的增殖能力得以维持。总之,经过进一步优化,CR 系统可能是 HCC 患者精确治疗的有用工具。