While mouse is currently the model system of choice for performing cell transplantation assays, novel xenograft models using zebrafish have several unique advantages: 1) small number of cells are required; 2) tumor formation and cell movement are easily visualized in the transparent animal; 3) small amount of drug is required per experiment; 4) results can be obtained from a statistically significant number of animals; and 5) results in zebrafish are amenable to quantitation using morphometric analysis.

We have developed zebrafish xenograft models by transplanting human cancer cells into zebrafish (Figure 1). Transplated cancer cells formed cell masses that were viable and proliferated over time in zebrafish. We also observed migration of cancer cells in zebrafish. Results from our experiments indicate that the zebrafish xenograft models are suitable for studying cancer cell proliferation and migration, and for testing potential anti-tumor drugs (Figure 2). Moreover, toxicity of potential anti-tumor drugs can be assessed in the same animals. Because many compounds that inhibit cancer cell proliferation also have deleterious effects on proliferating non-cancer cells, the toxicity information will help overcome a major obstacle in identifying potential anti-tumor drugs.

In addition to tumor models, cell transplantation models using zebrafish are also promising tools for stem cell research.

Figure 1. Cancer cell migration and tumor formation in zebrafish. A. Approximately 20 cells from the human colorectal adenocarcinoma cell line SW480 were injected into the yolks of 48 hpf zebrafish; one such embryo is shown here, 7 days later. A few cells remain at the former site of the now depleted yolk; the remainder of the cells are in the lining of the gut. B and C. Ten to fifteen cells from SW620, a cell line derived from a metastasis of SW480, were injected into the yolks of 48 hpf zebrafish. Shown here 7 days later, tumors have formed in the wall of the gut and cells have migrated (arrows) into the liver (B) and head (C).

Figure 2. Drug effects on transplanted human cancer cells in zebrafish: Cisplatin treatment reduced the growth of transplanted human prostate cancer cell line DU145 (Panels A, B and C), as compared to untreated controls (Panels D, E, and F). Arrows point to clusters of human cancer cells.