MMP10 is highly expressed in an osteosarcoma stem cell model and predicts poor prognosis

Osteosarcomas are high-grade primary bone malignancies that primarily affect children and young adults. Osteosarcoma stem cells (OSCs) play pivotal roles in the progression of malignancy and therapeutic resistance. In this study, we re-analyzed our previous RNA sequencing data from an OSC model and identified Matrix metalloproteinase 10 (MMP10) as among the most highly upregulated genes in OSC. We assessed the clinical relevance of MMP10 expression in patients with an osteosarcoma prognosis and elucidated its functional role in OSCs using knockdown approaches, both in vitro and in vivo. Among the MMP family members, MMP10 showed one of the highest expressions in OSCs, which was significantly associated with a poor prognosis in patients with high cancer stemness cell signatures. Knockdown of MMP10 caused a significant impairment of the tumor sphere formation and self-renewal capacities of OSCs in vitro, and suppressed tumor growth in a xenograft model. Bioinformatic analysis, based on gene set enrichment analysis, further revealed that a high expression of MMP10 was significantly associated with activation of the NF-κB signaling pathway in this high-stemness population. Collectively, these findings provided evidence that MMP-10 contributes to maintenance of the stem-like properties of osteosarcomas and could serve as a potential therapeutic target and candidate biomarker for osteosarcomas characterized by high stemness.