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

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 Petit-Paris (1) , Pierre Levillain (2) , Sevda Cordier-Dirikoc (3) , Nathalie Pedretti (3) , François Xavier Bernard (1, 3) , Jean Claude Lecron (1, 2) , Franck Morel (1) , Laure Favot (1)

1 LITEC [Poitiers] - Laboratoire Inflammation, Tissus épithéliaux et Cytokines [EA 4331]
2 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
3 QIMA Bioalternatives (QIMA Life Sciences)

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.

Mots clés: Oncostatin M; cytokine; Skin cancer; Tumor microenvironment; Immunotherapy

Domaines: Cancer

Marie Simonneau, Eric Frouin, Vincent Huguier, Cynthia Jermidi, Jean François Jégou, et al.. Oncostatin M is overexpressed in skin squamous-cell carcinoma and promotes tumor progression. Oncotarget, 2018, 9 (92), pp.36457-36473. ⟨10.18632/oncotarget.26355⟩. ⟨hal-04186396⟩