Human osteosarcoma cell secretome impairs neonatal mouse calvarial osteogenic cells functions and modifies the nanoparticles-derived protein profile

Osteosarcoma is the most common pediatric primary bone tumor, whose growth strictly relies on a complex interplay among tumor cells, resident cells, and the bone matrix. We investigated the effects of secretome collected from the human osteosarcoma cell line MNNG/HOS on mouse primary osteogenic cells, finding that prolonged exposure alters osteoblast phenotype and activity. MNNG/HOS secretome also reduces the production and release of collagen type I, the most abundant constituent of the bone matrix, and hinders osteoblast ability to form nodule of mineralization, compared to osteogenic cells treated with their own secretome. Given the crucial role exerted by secretome on tumor growth, we aimed also to determine whether osteosarcoma cells secretome can influence the osteoblast release of extracellular nanoparticles (NPs) as well as NPs protein cargo. Intriguingly, we found that MNNG/HOS secretome exerts a direct effect on osteoblast-NPs, reprogramming their protein cargo and subsequently influencing extracellular matrix composition and collagen formation, in favor of tumor progression. Overall, our findings indicate the ability of MNNG/HOS cells to fuel their own malignancy by deranging bone matrix composition and stimulating osteoblast-nanoparticles shuttling of osteosarcoma promoting factors.