Oncostatin M is overexpressed in skin squamous-cell carcinoma and promotes tumor progression

Abstract

// Marie Simonneau 1 , Eric Frouin 1, 2 , Vincent Huguier 1, 2 , Cynthia Jermidi 1, 2 , Jean François Jégou 1 , Julie Godet 2 , Anne Barra 1, 2 , Isabelle Paris 1, 2 , Pierre Levillain 2 , Sevda Cordier-Dirikoc 3 , Nathalie Pedretti 3 , François Xavier Bernard 1, 3 , Jean Claude Lecron 1, 2 , Franck Morel 1 and Laure Favot 1 1 LITEC, Université de Poitiers, Poitiers, France 2 CHU de Poitiers, Poitiers, France 3 Bioalternatives, Gençay, France Correspondence to: Laure Favot, email: laure.favot@univ-poitiers.fr Keywords: oncostatin M; cytokine; skin cancer; tumor microenvironment; immunotherapy Received: July 27, 2018     Accepted: November 01, 2018     Published: November 23, 2018 ABSTRACT Cutaneous squamous cell carcinoma (cSCC) is the second most common keratinocyte malignancy and accounts for 20% of skin cancer deaths. Cancer is closely related to inflammation, but the contribution of the tumor microenvironment to cSCC development is poorly understood. We previously showed that oncostatin M (OSM), a cytokine belonging to the IL-6 family, promotes normal keratinocyte proliferation and migration, skin inflammation, and epidermal hyperplasia, both in vitro and in vivo . Here, we show that OSM is overexpressed in human cSCC and is associated with type 1 immune polarization. In vitro , OSM induced STAT-3 and ERK signaling, modified the expression of genes involved in cytokine signaling, proliferation, inhibition of apoptosis, and immune responses, and promoted proliferation and migration of malignant keratinocyte PDVC57 cells. PDVC57 cells grafted in the skin of mice led to rapid cSCC development, associated with OSM expression by tumor-infiltrating neutrophils. Finally, the absence of OSM (OSM-KO mice) led to a 30% reduction of tumor size and reduced M2 polarization in the tumor microenvironment. Globally, these results support a pro-tumoral role of OSM in cSCC development and suggest that a new therapeutic approach targeting this cytokine could be considered.