title: Human melanoma progression in skin reconstructs : biological significance of bFGF.
abstract: Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Cells in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact. Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.
authors.affiliation: Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: F
authors.initials: F
authors.lastname: Meier
authors.forename: M
authors.initials: M
authors.lastname: Nesbit
authors.forename: M Y
authors.initials: MY
authors.lastname: Hsu
authors.forename: B
authors.initials: B
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Van Belle
authors.forename: D E
authors.initials: DE
authors.lastname: Elder
authors.forename: G
authors.initials: G
authors.lastname: Schaumburg-Lever
authors.forename: C
authors.initials: C
authors.lastname: Garbe
authors.forename: T M
authors.initials: TM
authors.lastname: Walz
authors.forename: P
authors.initials: P
authors.lastname: Donatien
authors.forename: T M
authors.initials: TM
authors.lastname: Crombleholme
authors.forename: M
authors.initials: M
authors.lastname: Herlyn
mesh_terms: D001485:Basement Membrane / Q000502:physiology; D002455:Cell Division; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000503:physiopathology; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology* / Q000503:physiopathology; D017768:Skin, Artificial; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000473:pathology
chemical_list: D016222:Fibroblast Growth Factor 2