Zebrafish xenotransplantation model for cancer stem-like cell study and high-throughput screening of inhibitors
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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.
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