Neural crest cell migration of mouse B16-F1 melanoma cells transplanted into the chick embryo is inhibited by the BMP-antagonist noggin.

Melanoma cells are derived from the neural crest and characterized by high migratory potential and invasive growth. To test the analogies between malignant and embryonic cell migration, in previous studies we transplanted melanoma cells and non-transformed mouse neural stem cells into the neural crest compartment of the chick embryo. Human and mouse melanoma cells spontaneously migrated along the neural crest pathways while emigration of neural stem cells was dependent on pre-treatment with BMP-2 (bone morphogenetic protein-2). In the embryo neural crest cell migration is induced by BMP and inhibited by its antagonist noggin. We tested whether the spontaneous neural crest cell migration of melanoma cells was dependent on their endogenously expressed BMP and could be inhibited by noggin. Mouse B16-F1 melanoma cells transfected with GFP-VASP (vasodilator-stimulated phosphoprotein) were cultured as aggregates and treated with BMP-2 or noggin. Untreated and treated aggregates were transplanted into the neural tube of the E2 chick embryo. Untreated and BMP-2-treated melanoma cells emigrated from the neural tube along with the chick host neural crest cells. Noggin-treated aggregates showed no emigration. We conclude that spontaneous emigration of melanoma cells depends on their constitutive overexpression of BMP, and that noggin efficiently suppresses the emigration of melanoma cells in the embryonic micro-environment, thus rendering noggin a promising agent for the inhibition of melanoma cell migration in vivo.