Department of Pediatric Hematology and Oncology, 2(nd) Medical Faculty, Charles University and University Hospital Motol, V Uvalu 84, 150 06 Prague, Czech Republic.
Neoplasma. 2012;59(6):737-46. doi: 10.4149/neo_2012_093.
Cancer stem cells (CSCs) form a small proportion of tumor cells that have stem cell properties: self-renewal capacity, the ability to develop into different lineages and proliferative potential. The interest in CSCs emerged from their expected role in initiation, progression and recurrence of many tumors. They are generally resistant to conventional chemotherapy and radiotherapy. There are two hypotheses about their origin: The first assumes that CSCs may arise from normal stem cells, and the second supposes that differentiated cells acquire the properties of CSCs. Both hypotheses are not mutually exclusive, as it is possible that CSCs have a diverse origin in different tumors. CD133+ cells (CD133 is marker of CSC in some tumors) isolated from NBL, osteosarcoma and Ewing sarcoma cell lines are resistant to cisplatin, carboplatin, etoposide and doxorubicin than the CD133- ones. Being resistant to chemotherapy, there were many attempts to target CSCs epigenetically including the use of histone deacetylase inhibitors. The diverse influence of valproic acid (histone deacetylase inhibitor) on normal and cancer stem cells was proved in different experiments. We have found an increase percentage of CD133+ NBL cells after their incubation with VPA in a dose that does not induce apoptosis. Further researches on CSCs and clinical application for their detection are necessary: (i) to define the CSC function in carcinogenesis, cancer development and their role in metastasis; (ii) to find a specific marker for CSCs in different tumors; (iii) to explain the role of different pathways that determine their behavior and (iv) to explain mechanisms of chemoresistance of CSCs.
癌症干细胞（CSC）形成一小部分具有干细胞特性的肿瘤细胞：自我更新能力、向不同谱系发展的能力和增殖潜能。对 CSC 的兴趣源于它们在许多肿瘤的起始、进展和复发中的预期作用。它们通常对常规化疗和放疗具有抗性。关于它们的起源有两种假设：第一种假设认为 CSC 可能来自正常干细胞，第二种假设认为分化细胞获得了 CSC 的特性。这两种假设并不相互排斥，因为在不同的肿瘤中，CSC 可能具有不同的起源。从神经母细胞瘤、骨肉瘤和尤文肉瘤细胞系中分离出的 CD133+细胞（CD133 是某些肿瘤中 CSC 的标志物）比 CD133-细胞对顺铂、卡铂、依托泊苷和阿霉素更具耐药性。由于对化疗具有抗性，因此人们尝试了许多针对 CSC 的表观遗传靶向治疗，包括使用组蛋白去乙酰化酶抑制剂。不同实验证明了丙戊酸（组蛋白去乙酰化酶抑制剂）对正常和癌症干细胞的不同影响。我们发现，在 VPA 孵育后，CD133+NBL 细胞的百分比增加，而 VPA 诱导的细胞凋亡没有增加。有必要对 CSC 进行进一步研究并将其用于临床检测：（i）定义 CSC 在致癌作用、癌症发展及其在转移中的作用；（ii）在不同肿瘤中找到 CSC 的特异性标志物；（iii）解释决定其行为的不同途径的作用；（iv）解释 CSC 化疗耐药性的机制。
