title: Skin equivalent: an attractive model to evaluate early melanoma metastasis.
abstract: The growth patterns and morphological phenotype of four human melanoma cell lines with different metastatic potentials were investigated in submerged and in air-exposed (skin equivalent) keratinocyte-melanoma cell co-cultures. In contrast to the submerged co-cultures, all four cell lines formed sharply demarcated tumour cell nests within the epidermal compartment of the skin equivalent model, with the morphology highly mimicking the in vivo situation. Differences among the melanoma cell lines tested were observed with respect to the number of clusters formed and the ability to exhibit invasive growth. Only the two metastatic cell lines were able to invade the dermal compartment. Screening of cellular adhesion molecules revealed that the expression patterns in different cell lines were heterogeneous and remained unchanged during the whole culture period, irrespective of whether the melanoma cells were located in the epidermal or dermal compartment. A correlation was found between expression of a lower number of different cellular adhesion molecules and the ability to acquire invasive growth capability. Our results indicate that melanoma cells exhibit a heterogeneous growth behaviour when co-cultured with human keratinocytes, and the air-exposed skin equivalent model was shown to be suitable for studying differences in growth patterns and potential invasive behaviour.
authors.affiliation: Department of Dermatology, Leiden University Medical Centre, The Netherlands.
authors.forename: S K
authors.initials: SK
authors.lastname: Dekker
authors.forename: R
authors.initials: R
authors.lastname: van Doorn
authors.forename: J
authors.initials: J
authors.lastname: Kempenaar
authors.forename: N A
authors.initials: NA
authors.lastname: Gruis
authors.forename: B J
authors.initials: BJ
authors.lastname: Vermeer
authors.forename: M
authors.initials: M
authors.lastname: Ponec
mesh_terms: D000388:Air; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division; D018920:Coculture Techniques; D003470:Culture Media; D000078404:Epidermal Cells; D006801:Humans; D007101:Immersion; D016023:Integrins / Q000032:analysis / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology*; D008544:Melanocytes / Q000737:chemistry / Q000473:pathology*; D008545:Melanoma / Q000737:chemistry / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology*; D017768:Skin, Artificial; D014407:Tumor Cells, Cultured / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; D003470:Culture Media; D016023:Integrins; D009363:Neoplasm Proteins