2. Academic Validation
  3. Senescent Epithelial Cells Serve as Invasive Growth Drivers in Ameloblastoma

Senescent Epithelial Cells Serve as Invasive Growth Drivers in Ameloblastoma

  • Lab Invest. 2025 Aug 6;105(11):104227. doi: 10.1016/j.labinv.2025.104227.
Hao Lin 1,  Jia-Jie Liang 1,  Chen-Xi Zhang 1,  Qi-Wen Man 2,  Rui-Fang Li 2,  Lin-Zhou Zhang 3,  Bing Liu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
  • 3 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China. Electronic address: Zhanglinzhou@whu.edu.cn.
  • 4 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. Electronic address: liubing9909@whu.edu.cn.
PMID: 40780542 DOI: 10.1016/j.labinv.2025.104227
Abstract

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.

Keywords

ameloblastoma; angiogenesis; cellular senescence; osteoclastogenesis; stemness.

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