並列タイトル等Interleukin-1α promotes matrix metalloproteinase-9expression, cellular motility, and local invasiveness ofameloblastoma cells
学位博士(歯学)
Doctor of Philosophy in Dental Science
一般注記博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
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.
Yusuke Ono, Takao Fuchigami, Michiko Kishida, Hirofumi Koyama, Mikio Iijima, Kazuki Oishi, Toshiro Kibe, Kiyohide Ishihata, Yoshiaki Nishizawa, Tohru Kiyono, Norifumi Nakamura, Shosei Kishida
Interleukin-1α promotes matrix metalloproteinase-9 expression, cellular motility, and local invasiveness of ameloblastoma cells
Oral Science International 2024;21:112–120.
https://doi.org/10.1002/osi2.1193
This is the peer reviewed version of the following article: [ https://onlinelibrary.wiley.com/doi/full/10.1002/osi2.1193 ], which has been published in final form at [ https://doi.org/10.1002/osi2.1193 ]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）