Oncostatin M is a leukocyte product that has been reported to have anti-proliferative effects directly on melanoma and other cancer cell lines in vitro. However, its function(s) in cancers in vivo appears complex and its roles in cancer growth in lungs are unknown. Here, we show that OSM promotes marked growth of tumour cells in mouse lungs. Local pulmonary administration of adenovirus vector expressing mouse OSM (AdOSM) induced >13-fold increase in lung tumour burden of ectopically delivered B16-F10 melanoma cells in C57BL/6 mice. AdOSM caused increases in tumour size (14 days post-challenge), whereas control vector (Addel70) did not. AdOSM had no such action in C57BL/6 mice deficient in the OSM receptor beta chain (OSMRb2/2), indicating that these effects required OSMRb expression on non-tumour cells in the recipient mice. AdOSM induced elevated levels of chemokines and inflammatory cells in the bronchoalveolar lavage (BAL) fluid, elevated arginase-1 mRNA levels (60-fold), and increased arginase-11immunostaining macrophage numbers in lungs. Adherent BAL cells collected from AdOSM-treated mice expressed elevated arginase-1 activity. In contrast to AdOSM-induced effects, pulmonary over-expression of IL-1b (AdIL-1b) induced neutrophil accumulation and iNOS mRNA, but did not modulate tumour burden. AdOSM also increased lung tumour load (>50-fold) upon ectopic administration of Lewis lung carcinoma (LLC) cells in vivo. However, in vitro, neither recombinant OSM nor AdOSM infection stimulated B16-F10 or LLC cell growth directly. We conclude that pulmonary over-expression of OSM promotes tumour growth, and does so through altering the local lung environment with accumulation of M2 macrophages.Cancer of the lung and bronchus is the leading cause of cancer-related deaths in the US and Canada 1 and has by far the poorest survival prognosis (40% 1 year, 17% 5 years) amongst major cancer types (prostate, colorectal, breast). In 2013, it is estimated that lung cancer will claim nearly 160,000 lives (approximately 30% of total deaths due to cancer) and that an additional 220,000 new cases will be reported in the US alone. Lung cancer is particularly difficult to treat, due in part to aggressive tumour growth, and thus new approaches are needed to supplement or augment current established therapeutic regimens. Many cancers are linked to conditions of chronic inflammation, such as inflammation associated with cigarette smoke or asbestos exposure, inflammation upon infection (i.e. Helicobacter pylori in stomach cancer, Hepatitis B and C in liver cancer), and inflammation can be induced by the tumour itself.2,3 Inflammation has indeed been implicated in mechanisms of tumourigenesis and cancer growth through modifying the tumour microenvironment (as reviewed in Refs. 4 and 5).Particular microenvironment conditions such as the recruitment of select cellular mediators of inflammation to the tumour site can support cancer growth. For instance, tumour-associated macrophages (TAM) can generate an immunosuppressive environment rich in...