title: Engineering melanoma progression in a humanized environment in vivo.
abstract: 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, faithfully recapitulating human disease initiation and progression. To this end, human melanoma cells were seeded into engineered human dermo-epidermal skin substitutes. Transplantation onto the back of immunocompromised rats 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 the tumor cells into their physiological microenvironment, transition of radial to vertical growth, and establishment of highly vascularized, aggressive tumors with dermal involvement. Because all cellular components can be individually accessed using this approach, it allows manipulation of the tumor cells, as well as of the keratinocyte and stromal cell populations. Therefore, in one defined model system, tumor cell-autonomous and non-autonomous pathways regulating human disease progression can be investigated in a humanized, clinically relevant context.
authors: Cell and Developmental Biology, Institute of Anatomy, University of Zurich, Zurich, Switzerland.
authors: Gregor
authors: G
authors: Kiowski
authors: Thomas
authors: T
authors: Biedermann
authors: Daniel S
authors: DS
authors: Widmer
authors: Gianluca
authors: G
authors: Civenni
authors: Charlotte
authors: C
authors: Burger
authors: Reinhard
authors: R
authors: Dummer
authors: Lukas
authors: L
authors: Sommer
authors: Ernst
authors: E
authors: Reichmann
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology; D004195:Disease Models, Animal; D000078404:Epidermal Cells; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D016867:Immunocompromised Host; D015603:Keratinocytes / Q000166:cytology; D008544:Melanocytes / Q000166:cytology; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D009924:Organ Culture Techniques / Q000379:methods*; D051381:Rats; D012878:Skin Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016038:Skin Transplantation; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000502:physiology*