Zebrafish as a model for Cancer. In recent years, zebrafish received strong attention from cancer researchers, after it was discovered that zebrafish can develop almost any type of cancer (13). A critical asset of zebrafish as a cancer model is that many tumors histologically resemble human tumors (14). In addition, more general cancer characteristics such as genomic instability, invasiveness, transplantability, and the existence of cancer stem cells (15) apply to zebrafish tumors as well, and many tumor suppressor genes and oncogenes have been conserved. Further, the development of fish lines harboring oncogenic transgenes and their amenability to genetic and pharmacological testing also made zebrafish a favorable model. Cancer progression in zebrafish recapitulates many aspects of human disease and opens the door for studies to identify genetic and chemical modifiers of cancer (14, 16-20). The development of xenograft models allow the propagation and visualization of human cancer cells engrafted in optically transparent zebrafish (21-25). Numerous mutant or tissue-specific transgenic cancer fish lines are available (14, 16-20). Zebrafish can also efficiently absorb anticancer agents directly from water which makes this organism appealing for screening these compounds (20, 26). Taken together, these studies validate zebrafish as a bona fide cancer model. Advanced melanoma is a devastating and lethal cancer (27). Melanoma arises from melanocytes, which are the pigment producing cells of human skin. Melanocytes can proliferate and give rise to various types of benign nevi, which are commonly referred to as moles. Transformed melanocytes can yield melanomas that initially grow radially in the epidermis. This is followed by the transition to a vertical growth phase that involves invasion through the basement membrane into the underlying dermis, preceeding metastasis. There are many areas of melanoma biology that are underexplored. For example, the steps by which a normal melanocyte becomes or generates a melanoma cell are largely unknown. How the disease subverts properties of normal melanocytes and their neural crest progenitors has been a topic of recent investigations, and this will be a fertile area of research in the future. Lastly, while great progress has been made in identifying genetic defects that contribute to melanoma (28), there are clearly many more genes that remain to be tied to this disease. And significant challenges in the clinical management of this disease remain. These ...
