title: Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment.
abstract: The clinical management of cutaneous melanoma would benefit significantly from a better understanding of the molecular changes that occur during melanocytic progression to a melanoma phenotype. To gain unique insights into this process, we developed a three-dimensional in vitro model that allows observations of normal human melanocytes interacting with a metastatic melanoma matrix to determine whether these normal cells could be reprogrammed by inductive cues in the tumor cell microenvironment. The results show the epigenetic transdifferentiation of the normal melanocytic phenotype to that of an aggressive melanoma-like cell with commensurate increased migratory and invasive ability with no detectable genomic alterations. Removal of the transdifferentiated melanocytes from the inductive metastatic melanoma microenvironment results in a reversion to their normal phenotype. However, a normal melanocyte microenvironment had no epigenetic influence on the phenotype of metastatic melanoma cells. This novel approach identifies specific genes involved in the transdifferentiation of melanocytes to a more aggressive phenotype, which may offer significant therapeutic value.
authors.affiliation: Children's Memorial Research Center and Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, IL 60614, USA.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Seftor
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brown
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Kirschmann
authors.forename: William W
authors.initials: WW
authors.lastname: Wheaton
authors.forename: Alexei
authors.initials: A
authors.lastname: Protopopov
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Yoganand
authors.initials: Y
authors.lastname: Balagurunathan
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: Richard E B
authors.initials: RE
authors.lastname: Seftor
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Hendrix
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008544:Melanocytes / Q000473:pathology* / Q000502:physiology*; D008545:Melanoma / Q000235:genetics* / Q000473:pathology* / Q000556:secondary; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000556:secondary