title: In-vitro melanoma models: invasive growth is determined by dermal matrix and basement membrane.
abstract: A critical first step in the metastatic progression of cutaneous melanoma, invasive growth into the dermal compartment, would ideally be studied in the proper three-dimensional tissue microenvironment. In this study, we compared the growth and behavior of four melanoma cell lines originating from primary and metastatic human cutaneous melanomas (AN, RU, M14, and WK) in in-vitro human skin equivalents (HSEs) generated with four different dermal matrices: human fibroblast-seeded rat tail collagen, human fibroblast-derived matrix (FDM), noncellular human de-epidermized dermis (DED), and a novel fully cellular human DED with an intact pre-existent basement membrane. Melanoma cells showed proliferation in all HSEs, indicating that the microenvironment formed in all HSEs studied here allows the growth of melanoma cells in concert with epidermal keratinocytes for multiple weeks in vitro. Melanoma cells did not affect epidermal proliferation and terminal differentiation. Growth of melanoma cells in the dermal compartment, as a measure of invasive potential, differs markedly between the four types of in-vitro human melanoma models. Notably, the growth of melanoma cells in the dermal matrix was observed in all HSEs cultured with cell lines originating from metastatic melanoma, except for cDED-based HSEs, and the growth of melanoma cells of nonmetastatic origin was observed in the dermal compartment of FDM-based HSEs. Our results show that the type of dermal equivalent and the presence of an intact basement membrane should be taken into consideration when studying melanoma invasion using in-vitro HSEs.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Suzan
authors.initials: S
authors.lastname: Commandeur
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Sparks
authors.forename: Hee-Lam
authors.initials: HL
authors.lastname: Chan
authors.forename: Linda
authors.initials: L
authors.lastname: Gao
authors.forename: Jacoba J
authors.initials: JJ
authors.lastname: Out
authors.forename: Nelleke A
authors.initials: NA
authors.lastname: Gruis
authors.forename: Remco
authors.initials: R
authors.lastname: van Doorn
authors.forename: Abdoelwaheb
authors.initials: A
authors.lastname: El Ghalbzouri
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D020405:Dermis / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D018328:Melanoma, Amelanotic / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000473:pathology*