IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
GALECTIN 7 PROMOTES CHEMICAL SKIN CARCINOGENESIS THROUGH INDUCTION OF MYELOID REGULATORY CELLS IN MICE
Autor/es:
PINTO, NICOLAS A.; BLIDNER, ADA; RABINOVICH, GABRIEL A.; MORALES, ROSA M.; CROCI, DIEGO O.; JUAN P. CERLIANI; GATTO, SABRINA G.; ABBA, MARTIN C.
Reunión:
Congreso; Reunion conjunta de sociedades de Biociencias; 2017
Resumen:
Skin immunity is finely regulated by a broad network of cytokines and growth factors present in the epidermis and dermis to maintain tissue homeostasis. Disruption of this cellular and molecular balance may trigger different skin inflammatory diseases including psoriasis and dermatitis or neoplastic transformations like squamous cell carcinoma. Galectins, a family of beta-galactoside proteins that signal via glycosylated receptors, have emerged as key regulators of immune cell homeostasis. Galectin-7 is abundant in keratinocytes and is tightly regulated in response to skin environmental stress, suggesting that its altered expression may contribute to skin disease. The aim of this study was to evaluate the role of Gal7 during skin carcinogenesis. Using bioinformatic analysis (Enrichr resource and Cytoscape´s plugins ClueGo/CluePedia) we found that several oncogenic drivers (SOX2, NRAS, FOS, CD44 and RAC1 among others) were up-regulated in transgenic mice (Tg46) over-expressing Gal7 under the K14 promoter as, compared to wild type (WT) and Gal7-deficient (Lgals7-/-, KO) mice. This expression profile positively correlated with a higher number of skin papillomas developed in the skin of Tg46 mice compared to WT or KO animals. Notably, these mice were more susceptible to two-stage induced-carcinogenesis and developed papillomas at day 45, whereas WT and KO animals developed skin lesions at day 53 and 60 respectively. Interestingly, Tg46 mice overexpressing Gal7 in keratinocytes exhibited a higher percentage of MDSC in the spleen compared to their WT counterpart. MDSCs purified from Tg46 mice showed enhanced immunosuppressive activity as compared to WT and KO MDSCs in in vitro lymphoproliferation assay. This enhanced immunosuppressive effect may account for increased tumor susceptibility in vivo. In conclusion, altered expression of Gal7 may contribute to skin carcinogenesis by favoring dysregulation of oncogenic drivers and promoting expansion of immunosuppressive MDSCs.