Melanoma innervation, noradrenaline and cancer progression in zebrafish xenograft model.

The tumor microenvironment, including the peripheral nervous system, plays a key role in regulating tumor biology, from initiation to cancer progression. Here, by modeling aggressive melanoma in larval zebrafish xenografts, we shed light on the dynamics of tumor innervation in the tumor microenvironment (TME). Axonogenesis and dendritogenesis were detected in the neurons surrounding the melanoma niche and neurogenesis was observed in the nearby population of the enteric nervous system. We also demonstrate the crucial role of noradrenaline in promoting melanoma progression with the dissemination and invasion of cancer cells to distant tissues. This zebrafish model will allow to uncover neural markers associated with melanoma progression to help in the design of innovative anti-neurogenic therapies targeting specifically the neuronal signals that regulate melanoma progression.