NELL1, or Neural EGF like-like molecule 1, is a secreted glycoprotein. It has nonneoplastic osteoinductive effects, regulating the extracellular matrix (ECM) in processes like osteogenesis [1].

Genetic deletion of NELL1 in human osteosarcoma (OS) cell lines significantly reduces invasive behavior. In xenograft mouse models, Nell1 deletion inhibits metastasis and improves survival, as also seen in p53/Rb-driven sarcomagenesis mouse models with conditional knockout of Nell1, which reduces tumor frequency and extends tumor-free survival. Transcriptomic and phosphoproteomic analyses suggest that NELL1 loss skews the expression of matricellular proteins associated with reduced FAK signaling [1].

In summary, NELL1 is a crucial secreted glycoprotein involved in osteogenesis and ECM regulation. Its gene knockout and conditional knockout in mouse models have revealed its significant role in osteosarcoma progression, highlighting its potential as a therapeutic target in this disease area.