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The Neural Crest and Cancer: A Developmental Spin on Melanoma

Kulesa, P.M., Morrison, J.A., Bailey, C.M.

Neural crest (NC) cells undergo an epithelial-to-mesenchymal transition (EMT) in order to exit from the dorsal neural tube. Similarly, ancestrally-related melanoma cells employ an EMT-like event during the initial stages of metastasis to dissociate from surrounding keratinocytes. Whether the molecular pathogenesis and cellular dynamics of melanoma metastasis resemble the embryonic NC invasion program is unclear. Here, we highlight advances in our understanding of tumor cell behaviors and plasticity, focusing on the relationship between melanoma and the neural crest invasion programs. We summarize recent discoveries of neural crest cell guidance and emerging in vivo imaging strategies that permit single cell resolution of fluorescently labeled tumor cells, with a focus on our recently developed in vivo chick embryo transplant model. Crucial to the molecular pathogenesis of metastasis, we highlight advances in gene profiling of small cell numbers, including our novel ability to gather gene expression information during distinct stages of melanoma invasion. Lastly, we present preliminary details of a comparison of specific genetic pathways associated with the early phases of melanoma invasion and known neural crest induction and migration signals. Our results suggest that malignant melanoma cells hijack portions of the neural crest program to promote plasticity and facilitate metastasis. In summary, there is considerable power in combining an in vivo model system with molecular analysis of gene expression, within the context of established developmental signaling pathways, to identify and study the molecular mechanisms of metastasis.

Citation

Kulesa, P.M., Morrison, J.A., Bailey, C.M. "The Neural Crest and Cancer: A Developmental Spin on Melanoma" Cells Tissues Organs (2015): 198