Work

Senescent vascular endothelial cells promote oral squamous cell carcinoma progression through complement C3 activation

Year: 2025

Type: article

Abstract: OBJECTIVE: The tumour microenvironment (TME) plays a critical role in therapeutic response and clinical outcomes in cancer. Senescent stromal cells have been shown to promote tumour progression; however, the role of senescent vascular endothelial cells (VECs) in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we aimed to explore the effects and potential mechanisms of senescent VECs in OSCC progression. DESIGN: Cisplatin was used to induce senescence in two endothelial cell lines. Senescence-associated β-galactosidase (SA-β-gal) staining, immunoblotting, cell cycle and proliferation assays, and migration and invasion assays were performed to access senescence development and biological behavior. Additionally, RNA sequencing analysis, multiplex immunohistochemical staining, immunoblotting, and xenograft mouse models were used to investigate the senescence-associated secretory phenotype of senescent VECs during OSCC progression and its potential molecular mechanisms. RESULTS: Cisplatin-induced senescent VECs exhibited senescence-related changes, including positive SA-β-gal expression and upregulation of p16, p21, and p53, along with attenuated proliferation and migration. Notably, cisplatin-induced VEC senescence promoted OSCC cell proliferation, migration, and invasion by activating complement C3. Increased gene and protein levels of C3 were observed in cisplatin-treated senescent VECs. Inhibition of C3 in vitro and in vivo reduced OSCC cell proliferation and invasion. CONCLUSION: Senescent VECs induced by cisplatin promote OSCC proliferation and invasion through complement C3 activation. Targeting complement C3 in senescent VECs may offer a novel therapeutic strategy for OSCC treatment.

Source: Archives of Oral Biology

DOI: 10.1016/j.archoralbio.2025.106242

Authors: Fangqi Jing, Jingtian Mu, Junjiang Liu, Can Hu, Fanglong Wu, Qinghong Gao

Institutions: Sichuan University, State Key Laboratory of Oral Diseases

Language: English

Topic: Telomeres, Telomerase, and Senescence

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,760