Gene expression signature for spontaneous cancer regression in melanoma pigs.
Incomplete spontaneous regression of melanoma is common. However, complete melanoma regression is still a very rare phenomenon. Because melanoma is the most immunogenic human malignancy, the mechanisms leading to regression, based on accumulative evidence, are the host's immune responses. Unfortunately, therapies aiming to enhance the patient's natural immunity against melanoma have yet to meet their expectations. Reasons for failure include various immune escape mechanisms, induced by the tumor, that subsequently lead to tolerance. Here, we performed time-dependent gene expression profiling to unravel molecular changes involved in the transition of progressive melanoma to complete tumor regression using a porcine model. The melanoblastomabearing Libechov minipigs are highly suitable for this study because these animals exhibit naturally occurring and regressing melanomas. We were able to identify a molecular signature of the melanoma regression process. Genes regulated in this signature were associated with 1) cell cycle, 2) immune response, and 3) melanocyte differentiation. These genes may shed light on molecular mechanisms involved in complete melanoma regression and indicate what improvements are needed for successful antimelanoma therapy.
Rambow
Florian
F
INRA, UMR 314, Laboratoire de Radiobiologie et d'Etude du Génome, F-78350 Jouy-en-Josas, France. florian.rambow@jouy.inra.fr
Piton
Guillaume
G
Bouet
Stephan
S
Leplat
Jean-Jaques
JJ
Baulande
Sylvain
S
Marrau
Angelique
A
Stam
Mark
M
Horak
Vratislav
V
Vincent-Naulleau
Silvia
S
D000818:Animals; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005802:Genes, MHC Class II; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009365:Neoplasm Regression, Spontaneous / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D013552:Swine / Q000235:genetics*; D013997:Time Factors