Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment
Kulesa, P.M., Kaselmeier-Kulesa, J.C., Teddy, J.M., Margaryan, N.V., Seftor, E.A., Seftor, R.E.B., and Hendrix, M.J.C. Proc. Nat. Acad. Sci. site, 103, 3752-3757 (March 7, 2006).
This work extends the study of tumor cell plasticity to a new model, the chick embryo, by demonstrating that the microenvironment alters phenotypic expression of transplanted human metastatic melanoma cells. Specifically, the results show that melanoma cells transplanted into 7- to 9-somite chick embryos do not form tumors, but rather, express phenotypic traits resembling those of neural crest cells (NCCs). After 48 hours, the cells migrate into the mesoderm layer and subsequently distribute along the cranial NCC migratory pathways, including the dorsal root and sympathetic ganglia. Moreover, they tend not to spread laterally, but follow the normal cells’ trajectories. Their migration appears to follow cues provided by the microenvironment, rather than the indigenous NCCs themselves, as ablation of the NCCs had no effect on melanoma cell distribution.
The transplanted melanoma cells exhibited morphological features closely resembling those of chick NCCs in the formation of filopodial connections between adjacent cells and linear chain-like arrays. However, differences were also observed, notably less hairy and bipolar shaped-morphologies. To determine whether the embryonic microenvironment also resulted in the expression of phenotype-specific genes, a study looked for several markers of melanocytes, neurons, and glia that the original metastatic melanoma cells did not exhibit. Small numbers of the transplanted cells expressed a melanocyte-specific marker (MART-1), while others tested positive for a neuronal marker (TuJ1).
Overall, the results indicate that metastatic melanoma cells transplanted into chick embryos create a model for studying signals that drive normal embryogenesis and factors that might prove useful in combating certain types of cancer.
Message posted by: Keith Markey
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