IGF2 knockout reduces but does not abolish osteosarcoma growth in vitro and in vivo.

Insulin-like growth factor 2 (IGF2) is implicated in osteosarcoma, but direct functional evidence of its role is lacking. Here, we used CRISPR-Cas9 to knock out IGF2 in Saos2 osteosarcoma cells. Knockout cells showed reduced proliferation in vitro which was fully restored by exogenous IGF2. In vivo, knockout xenografts reached only ~25% of wild-type tumor volume. Furthermore, transcriptomic analysis revealed depletion of angiogenesis-related genes but no major changes in IGF2 pathway components. Finally, while integration with receptor dependency data suggested alternative signaling pathways, IGF2 loss remained functionally limiting. These findings demonstrate that IGF2 promotes osteosarcoma proliferation and tumor growth but is not strictly essential for survival.