Cancer testis antigens in human melanoma stem cells: expression, distribution, and methylation status.

Journal of Cellular Physiology
Luca SigalottiMichele Maio

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.

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Citations

Feb 18, 2009·Cancer Immunology, Immunotherapy : CII·Craig GedyeIan D Davis
Oct 29, 2009·Cancer Immunology, Immunotherapy : CII·Luca SigalottiMichele Maio
Mar 23, 2013·Clinical & Experimental Metastasis·Antonia BusseUlrich Keilholz
Dec 2, 2008·Pigment Cell & Melanoma Research·Hunter W Richards, Estela E Medrano
Jun 15, 2010·Journal of Translational Medicine·Luca SigalottiMichele Maio
Aug 2, 2008·Breast Cancer Research : BCR·Brian J MorrisonJ Alejandro Lopez
Dec 23, 2010·Immunotherapy·Flora IovinoMatilde Todaro
Oct 4, 2013·Immunotherapy·Elisabetta FrattaMichele Maio
Jan 5, 2014·Pharmacology & Therapeutics·Luca SigalottiMichele Maio
Mar 9, 2012·Clinical & Developmental Immunology·Trudy StraetemansReno Debets
Aug 30, 2014·Advances in Medical Sciences·Mariusz Z RatajczakMarcin Moniuszko
Feb 12, 2010·Expert Opinion on Biological Therapy·Miriam CoccorisReno Debets
Apr 28, 2010·Expert Opinion on Biological Therapy·Morten Frier GjerstorffHenrik Jorn Ditzel
Oct 28, 2008·Seminars in Immunology·Michelle A NellerChristopher W Schmidt
Oct 29, 2010·Clinical & Developmental Immunology·Heath A Smith, Douglas G McNeel
Oct 3, 2009·Annals of the New York Academy of Sciences·Tobias Schatton, Markus H Frank
Feb 4, 2010·Journal of Cellular Physiology·Elisabetta FrattaMichele Maio
Mar 17, 2017·Journal of Molecular Biology·Anna K Lee, Patrick Ryan Potts
Oct 17, 2017·Immunotherapy·Sepideh Faramarzi, Soudeh Ghafouri-Fard
Sep 11, 2008·Melanoma Research·Irina N MikhaylovaAnatoly Y Baryshnikov
Feb 13, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aaron P RapoportCarl H June
Feb 1, 2011·Archives of Biochemistry and Biophysics·Neehar BhatiaB Jack Longley

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