Senescent Epithelial Cells Serve as Invasive Growth Drivers in Ameloblastoma

Cellular senescence and its associated microenvironment play a pivotal role in tumor initiation and progression. Although ameloblastoma (AM) is classified as a benign tumor, it is characterized by local invasiveness and a high recurrence rate. In this study, we identified a distinct population of senescent epithelial cells using senescence-associated β-galactosidase staining and explored the role of this subpopulation in AM progression. The CellChat tool was utilized to map intercellular communication networks, revealing that this senescent cell cluster promotes stemness in neighboring cells and drives angiogenesis and osteoclastogenesis, which was subsequently confirmed by a series of in vitro experiments. Moreover, conditioned medium from these senescent cells significantly enhanced tumor growth in patient-derived organoids. Clinical data further demonstrated that elevated levels of cellular senescence were strongly associated with greater tumor invasiveness and poorer prognosis in AM patients. In conclusion, our findings suggest that targeting this specific subset of senescent epithelial cells may offer a novel therapeutic approach for AM management, potentially reducing tumor aggressiveness and recurrence.