Zebrafish xenotransplantation model for cancer stem-like cell study and high-throughput screening of inhibitors
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.
KeywordsZebrafish Cancer stem-like cell Xenotransplantation
We thank M. Ariyoshi and S. Ichikawa for their assistance in the experiments and breeding the fish and R. Ikeyama and Y. Tamura for the secretarial assistance.
Conflicts of interest
This work was supported in part by the Japan Science and Technology Agency, KAKENHI of Grants-in-Aid for Scientific Research, and the New Energy and Industrial Technology Development Organization.
T.T. and Y.S. conceived and designed the study. B.Z., J.K., Y.S., N.U., and Y.N. performed the assays and analyzed the data. T.N, T.S., and T.M. performed chemical synthesis assays. B.Z. wrote the paper.
- 10.Kruczynski A, Hill BT: Classic in vivo cancer models: three examples of mouse models used in experimental therapeutics. Curr Protoc Pharmacol. 2002. Chapter 5: Unit5. 24.Google Scholar
- 21.Yang IH, Lee D, Lee SH, Kang JY. Characterization of proteolytically digested zebrafish chorion as extracellular matrix. Conf Proc: IEEE Eng Med Biol Soc. 2008;2008:1837–40.Google Scholar
- 30.Rudin CM, Salgia R, Wang X, Hodgson LD, Masters GA, Green M, et al. Randomized phase II study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103. J Clin Oncol: Off J Am Soc Clin Oncol. 2008;26:870–6.CrossRefGoogle Scholar