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Aim: Although ameloblastoma is a benign tumor, its local invasiveness and recurrence rate are both high. Thus, the regulation of the invasiveness of ameloblastoma cells into the surrounding tissue is required to understand its pathogenesis. Ameloblastoma cells secrete several matrix metalloproteinases (MMPs); however, the factors inducing their secretion remain unclear. We previously suggested that interleukin (IL)‐1α derived from ameloblastoma cells triggers the production of inflammatory cytokines by stromal fibroblasts. In this study, we estimated whether IL‐1α affects the behavior of ameloblastoma cells. Methods: The gene expression of MMP‐9 was assessed by real‐time reverse transcription–polymerase chain reaction (RT‐PCR). The secretion of MMP‐9 was assessed by enzyme‐linked immunosorbent assay (ELISA). The motility of AM‐3 ameloblastoma and Raw264.7 （macrophage derived cells） cells and the invasiveness of AM‐3 cells were calculated using the Boyden chamber. The invasiveness of AM‐3 cells toward human foreskin fibroblast (HFF)‐2 fibroblasts were assessed using modified double‐layered collagen gel hemisphere (DL‐CGH). Results: The mRNA expression and secretion of MMP‐9 by AM‐3 ameloblastoma cells were significantly increased by IL‐1α stimulation. The motilities of AM‐3 and RAW264.7 macrophage derived cells and the invasiveness of AM‐3 cells were significantly enhanced by IL‐1α and suppressed by an IL‐1 receptor antagonist (IL‐1Ra). The invasiveness of AM‐3 cells towards HFF‐2 fibroblasts in a DL‐CGH model was suppressed by a treatment with IL‐1Ra or an anti‐IL‐1α neutralizing antibody. Conclusion: IL‐1α itself or the IL‐1α‐dependent production of unidentified chemo attractants by stromal cells may be important for the local invasiveness of ameloblastoma cells, and IL‐1α might be a therapeutic target of the ameloblastoma. [ABSTRACT FROM AUTHOR]