Human to mouse melanoma xenografts are widely used in melanoma research because they seem to recapitulate the phenotypes occurring in the stage IV patients with melanoma.

In metastatic melanoma, brain metastases are diagnosed in 40–60% of patients and can be found in up to 90% at autopsy 3. In stage IV, therapeutic options are poor and overall survival is reduced to 6–9 months in untreated patients and to 5 months after occurrence of brain metastases 1, 2. The chick embryo model can be used for molecular studies of early phases of melanoma brain metastasis.Ĭutaneous melanoma is a highly aggressive malignancy with increasing incidence. Penetration of the roof plate epithelium, tumor formation and invasion of surrounding tissues by single cells can reliably be reproduced. The central tumor in the roof plate of the chick embryo rhombencephalon resembles a metastatic nodule in the patients with melanoma. Maximally invasive cells formed continuous tracks via vessels and along nerve fibres. Cell lines with different invasive properties retained their graded invasive behaviour.

From the tumor, single cells invaded the mesenchyme and blood vessels.

Although after 48 h melanoma cells invaded the rhombencephalic roof plate profusely at both sides, after 96 h typically one large tumor developed in the midline between roof plate and the dorsal surface epithelium. Local invasion occurred not in the ventral differentiating neural epithelium but only in the roof plate. Only melanoma cells in newly formed aggregates or when attached to the dorsal roof plate escaped apoptosis. The majority of the cells injected into the embryonic liquor cavity perished. After 48 and 96 h, tumor formation was studied in serial paraffin sections with melanoma-specific HMB45 and human-specific MIB1 proliferation markers. Patient-derived melanoma cells and established melanoma cell lines were injected into the rhombencephalic brain vesicle of the two-day-chick embryo. Here, we describe invasive growth and the development of melanoma metastases from suspensions of human melanoma cells in the brain of the chick embryo. Malignant melanoma has the highest propensity to metastasize to the brain of all primary neoplasms in adults.

96 Hour Chick Embryo Serial Section