title: Cancer testis antigens in human melanoma stem cells: expression, distribution, and methylation status.
abstract: Neoplastic populations with stem cell potential have been most recently identified in human cutaneous melanoma, and initially characterized for their phenotypic profile. Being melanoma stem cells (MSC) the most desirable target of therapeutic intervention, we asked whether they express the epigenetically-regulated cancer testis antigens (CTA) on which melanoma immunotherapy is increasingly focusing. Reverse transcription-PCR analyses identified the presence of the large majority of investigated CTA (i.e., MAGE, GAGE, NY-ESO, and SSX families) in different MSC populations. MSC expressed MAGE-A proteins as detected by western blot; noteworthy, the distribution of MAGE-A proteins was highly homogeneous within given MSC populations as shown by confocal immunofluorescence. Promoter methylation studies unveiled a homogeneously-demethylated MAGE-A3 promoter that paired MAGE-A3 expression in MSC. Altogether these findings demonstrate that MSC can be efficiently targeted by CTA-directed immunotherapeutic approaches, and suggest that epigenetic patterns most likely drive the expression of CTA in MSC as previously shown for melanoma cells.
authors.affiliation: Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Sigalotti
authors.forename: Alessia
authors.initials: A
authors.lastname: Covre
authors.forename: Susan
authors.initials: S
authors.lastname: Zabierowski
authors.forename: Benjamin
authors.initials: B
authors.lastname: Himes
authors.forename: Francesca
authors.initials: F
authors.lastname: Colizzi
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Natali
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D013737:Testis / Q000276:immunology*; D014018:Tissue Distribution
chemical_list: D000951:Antigens, Neoplasm