title: Three-Dimensional In Vitro Skin and Skin Cancer Models Based on Human Fibroblast-Derived Matrix.
abstract: Three-dimensional in vitro skin and skin cancer models help to dissect epidermal-dermal and tumor-stroma interactions. In the model presented here, normal human dermal fibroblasts isolated from adult skin self-assembled into dermal equivalents with their specific fibroblast-derived matrix (fdmDE) over 4 weeks. The fdmDE represented a complex human extracellular matrix that was stabilized by its own heterogeneous collagen fiber meshwork, largely resembling a human dermal in vivo architecture. Complemented with normal human epidermal keratinocytes, the skin equivalent (fdmSE) thereof favored the establishment of a well-stratified and differentiated epidermis and importantly allowed epidermal regeneration in vitro for at least 24 weeks. Moreover, the fdmDE could be used to study the features of cutaneous skin cancer. Complementing fdmDE with HaCaT cells in different stages of malignancy or tumor-derived cutaneous squamous cell carcinoma cell lines, the resulting skin cancer equivalents (fdmSCEs) recapitulated the respective degree of tumorigenicity. In addition, the fdmSCE invasion phenotypes correlated with their individual degree of tissue organization, disturbance in basement membrane organization, and presence of matrix metalloproteinases. Together, fdmDE-based models are well suited for long-term regeneration of normal human epidermis and, as they recapitulate tumor-specific growth, differentiation, and invasion profiles of cutaneous skin cancer cells, also provide an excellent human in vitro skin cancer model.
authors.affiliation: 1 Department of Genetics of Skin Carcinogenesis, German Cancer Research Center (DKFZ) , Heidelberg, Germany .
authors.forename: Manuel
authors.initials: M
authors.lastname: Berning
authors.affiliation: 1 Department of Genetics of Skin Carcinogenesis, German Cancer Research Center (DKFZ) , Heidelberg, Germany .
authors.forename: Silke
authors.initials: S
authors.lastname: Prätzel-Wunder
authors.affiliation: 2 Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa , Iowa City, Iowa.
authors.forename: Jackie R
authors.initials: JR
authors.lastname: Bickenbach
authors.affiliation: 1 Department of Genetics of Skin Carcinogenesis, German Cancer Research Center (DKFZ) , Heidelberg, Germany .|3 IUF-Leibniz Research Institute for Environmental Medicine , Düsseldorf, Germany .
authors.forename: Petra
authors.initials: P
authors.lastname: Boukamp
mesh_terms: D002452:Cell Count; D020405:Dermis / Q000166:cytology; D018450:Disease Progression; D000078404:Epidermal Cells; D004848:Epithelium / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D015603:Keratinocytes / Q000166:cytology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008954:Models, Biological; D018307:Neoplasms, Squamous Cell / Q000473:pathology; D010641:Phenotype; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology*; D017768:Skin, Artificial
chemical_list: D020782:Matrix Metalloproteinases