Zhang Beibei, Shimada Yasuhito, Kuroyanagi Junya, Nishimura Yuhei, Umemoto Noriko, Nomoto Tsuyoshi, Shintou Taichi, Miyazaki Takeshi, Tanaka Toshio
Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan.
Tumour Biol. 2014 Dec;35(12):11861-9. doi: 10.1007/s13277-014-2417-8. Epub 2014 Sep 11.
Xenotransplantation studies are important tools for studying cancer biology, especially for assaying tumor cell malignancy and providing cancer information in vivo. Cancer stem-like cells (CSCs) have been identified in many cancer types to drive tumor growth and recurrence, from "keeping" to "keep" resistant to chemotherapy and radiation therapy. In this study, we developed the xenotransplantation of CSCs derived from the leukemia and solid tumor cell lines using the zebrafish models. In adult zebrafish, we investigated that the xenografted leukemia stem cells (LSCs) from K562 cells could proliferate in vivo and keep the cancer property by re-transplantation. As for the solid tumor, these CSCs from DU145 cells (human prostate cancer) and HepG2 cells (human liver cancer) could form the tumor mass and even metastasis after xenotransplantation. In addition, the zebrafish embryos with CSC xenotransplantation could evaluate docetaxel in vivo efficiently and be available to screen the novel inhibitors by high-throughput manner. In summary, these zebrafish xenotransplantation models devote a good platform for the CSC mechanism investigation and anti-CSC inhibitor screening.
异种移植研究是研究癌症生物学的重要工具，特别是用于测定肿瘤细胞的恶性程度并在体内提供癌症信息。在许多癌症类型中都已鉴定出癌症干细胞（CSCs），它们可驱动肿瘤生长和复发，从“保持”到“持续”对化疗和放疗产生抗性。在本研究中，我们利用斑马鱼模型开发了源自白血病和实体瘤细胞系的癌症干细胞的异种移植。在成年斑马鱼中，我们研究了来自K562细胞的异种移植白血病干细胞（LSCs）在体内的增殖情况，并通过再次移植保持癌症特性。对于实体瘤，来自DU145细胞（人前列腺癌）和HepG2细胞（人肝癌）的这些癌症干细胞在异种移植后可形成肿瘤块甚至转移。此外，进行癌症干细胞异种移植的斑马鱼胚胎能够在体内有效评估多西他赛，并可通过高通量方式筛选新型抑制剂。总之，这些斑马鱼异种移植模型为癌症干细胞机制研究和抗癌症干细胞抑制剂筛选提供了一个良好的平台。
