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- Angiotropism and extravascular migratory metastasis in cutaneous and uveal melanoma progression in a zebrafish model
Angiotropism and extravascular migratory metastasis in cutaneous and uveal melanoma progression in a zebrafish model
Authors
Giulia Fornabaio, Raymond L. Barnhill, Claire Lugassy, Laurent A. Bentolila, Nathalie Cassoux, Sergio Roman-Roman, Samar Alsafadi, Filippo Del Bene
Abstract
Abstract
Cutaneous melanoma is a highly aggressive cancer with a propensity for distant metastasis to various organs. In contrast, melanoma arising in pigmented uveal layers of the eye metastasizes mostly in the liver. The mechanisms of these metastases, which are ultimately resistant to therapy, are still unclear. Metastasis via intravascular dissemination of tumour cells is widely accepted as a central paradigm. However, we have previously described an alternative mode of tumour dissemination, extravascular migratory metastasis, based on clinical and experimental data. This mechanism is characterised by the interaction of cancer cells with the abluminal vascular surface, which defines angiotropism. Here, we employed our 3D co-culture approach to monitor cutaneous and uveal human melanoma cells dynamics in presence of vascular tubules. Using time-lapse microscopy, we evaluated angiotropism, the migration of tumour cells along vascular tubules and the morphological changes occurring during these processes. Cutaneous and uveal melanoma cells were injected in zebrafish embryos in order to develop xenografts. Employing