Loss of Numbl protein in osteosarcoma is associated with metastasis and poor survival

Objective: Osteosarcoma is the most common primary malignant bone tumor. Conventional osteosarcoma is a primary intramedullary high grade malignant tumor, which occurred largely in children and young adult. Although combined treatment including adjuvant and neoadjuvant chemocherapy plus surgery has greatly improved survival of patients, the prognosis is poor with an initial mortality of 80%. There are abundant studies exploring the pathogenesis of osteosarcoma, however, the molecular mechanisms involved in the carcinogenesis, progression and prognosis are still unknown. Numbl, as a conserved homolog of Drosophila Numb, has been implicated in early development of the nervous system. Recently, its role in migration and invasion of tumors has been concerned. Methods: In this study, we investigated the expression of Numbl protein in a set of formalin fixed and paraffin embedded osteosarcoma tissue samples by using a specific anti-Numbl antibody. The relationship between the expression of Numbl and clinicopathologic parameters was analyzed. Results: We found that the expression level of Numbl protein reduced in osteosarcoma cells and down-regulation of Numbl was associated with the metastasis and a poor survival. Conclusions: Our data indicate that Numbl may be a molecular marker for prognosis and a potential therapeutic target in osteosarcoma.