Osteosarcoma, the most common primary malignant bone tumor, disrupts bone homeostasis by altering the surrounding microenvironment. Recent evidence highlights the critical role of the tumor secretome—comprising cytokines, growth factors, and extracellular vesicles—in modulating nearby osteogenic cells and influencing biomaterial interactions.
In this study, neonatal mouse calvarial osteogenic cells were exposed to the secretome derived from human osteosarcoma cells. Results revealed impaired osteogenic functions, including reduced proliferation, diminished alkaline phosphatase activity, and compromised mineralization capacity. These findings suggest that soluble tumor-derived factors interfere with normal bone-forming cell differentiation and activity, thereby contributing to the osteolytic nature of osteosarcoma.
Furthermore, the osteosarcoma secretome modified the protein corona of nanoparticles, a critical determinant of nanoparticle–cell interactions. Mass spectrometry-based proteomic profiling demonstrated altered adsorption of specific proteins, including extracellular matrix components and signaling molecules, onto nanoparticles incubated with osteosarcoma-conditioned media. Such changes could significantly impact nanoparticle uptake, biodistribution, and therapeutic efficacy in the osteosarcoma microenvironment.
Together, these findings provide new insights into how the osteosarcoma secretome not only hampers bone-forming cell function but also reshapes the bio–nano interface. This dual effect highlights the importance of considering tumor-derived secreted factors when designing therapeutic strategies and nanomedicine approaches for osteosarcoma.