An efficient method to generate xenograft tumor models of acute myeloid leukemia and hepatocellular carcinoma in adult zebrafish.

Zebrafish is emerging as a promising model for the study of human cancers. Several xenograft models of zebrafish have been developed, particularly in larval stages (<48 h post fertilization) when the immune system of fish is not developed. However, xenografting in adult zebrafish requires laborious and transient methods of immune suppression (γ- irradiation or dexamethasone) that limits engraftment and survival of the tumor or fail to recapitulate specific characteristics of malignancies. Thus, the availability of a simple protocol to successfully engraft adult zebrafish, remains a challenge. The current study addresses this limitation and describes a robust method of xenografting in adult zebrafish. We describe a protocol that involves pre-conditioning of Casper, a pigmentation mutant of zebrafish with busulfan that led to a higher rate of engraftment of hepatocellular carcinoma and acute myeloid leukemia cells. To further ascertain the homing characteristics of the injected cancer cells, we transplanted adult zebrafish by two routes of administration and then studied their compartmentalization. This model presents a valuable alternative to rodents to study the biology of these cancers and also a cost-effective platform for evaluation of potential anti-cancer agents.