Osteopontin as an airway epithelial tumor promoter

Osteopontin (secreted phosphoprotein 1; SPP1) expression has been identified in human lung cancer and has been linked with enhanced tumor progression. To examine its functional role, we induced lung tumors by repetitive urethane or MCA/BHT lung carcinogens in C57BL/6 mice lacking both (Spp1-/-), one (Spp1+/-), or no (Spp1+/+) copy of the endogenous Spp1 gene. Primary end-points were lung tumor number and size; secondary end-points were SPP1 expression, epithelial cell survival, carcinogen-induced inflammation, and angiogenesis. Data are presented as mean±SD. Compared with Spp1+/+ mice (n=22), Spp1-/- mice (n=25) developed dramatically fewer and significantly smaller lung tumors in response to urethane, while Spp1+/- mice (n=12) behaved similar to Spp1-/- mice (number/diameter of lung tumors in Spp1+/+, Spp1+/-, and Spp1-/- mice, respectively: 16.1±12.7/1.2±0.3 mm, 2.4±2.3/0.9±0.2 mm, and 1.3±1.6/0.7±0.2 mm; P These studies were supported by a European Research Council Starting Independent Investigator Grant (#260524).