Oral communication, CS15 / C67

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Engineering melanoma progression in a humanized environment in vivo

BACKGROUND: To overcome the lack of effective therapeutics for aggressive melanoma, new research models closely resembling the human disease are required. Here we report the development of a fully orthotopic, humanized in vivo model for melanoma exactly recapitulating human disease initiation and progression. METHODS: Human melanoma cells were seeded together with human keratinocytes onto collagen type I hydrogels, previously populated with human dermal fibroblasts. The engineered human dermo-epidermal skin substitutes were transplanted onto the back of immuno-compromized rats. RESULTS: The transplantations consistently resulted in the development of melanoma displaying the hallmarks of their parental tumors. Importantly, all initial steps of disease progression were recapitulated, including the incorporation of tumor cells into their physiological microenvironment, transition of radial to vertical growth, and the establishment of highly vascularized, aggressive tumors with dermal involvement. Because all cellular components can be individually accessed using this approach, it allows manipulation of tumor cells as well as of keratinocyte and stromal cell populations. CONCLUSION: This is a model of tissue engineered human skin that allows melanoma formation and investigation of local tumor progression as well as of those mechanisms leading to metastasis.

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