KEY TAKEAWAYS
- The study aimed to clarify how ANE influences cells in the oral microenvironment to promote cancer.
- Researchers reveal areca nut promotes M2 macrophage differentiation and cytokine secretion, driving oral carcinogenesis.
Betel quid and its main ingredient, areca nut, are recognized by the IARC as major risk factors for oral cancer and head and neck cancer. Areca nut extract (ANE) exposure has been associated with the progression of oral potentially malignant disorders (OPMD) and their malignant transformation into oral squamous cell carcinoma (OSCC). However, the precise mechanism by which ANE affects other cell types in the oral microenvironment to promote head and neck carcinogenesis remains unclear.
Shyng-Shiou F Yuan and the team aimed to uncover the mechanisms by which ANE influences other cells in the oral microenvironment to promote oral carcinogenesis.
The study immunoprofiled macrophages associated with OPMD and OSCC using immunohistochemical and immunofluorescence staining. Researchers performed phosphokinase and cytokine arrays, along with western blotting, to uncover the underlying mechanisms. Transwell assays were conducted to assess the migration-promoting effect of ANE. Finally, a hamster model was used to confirm ANE’s in vivo effects.
Results showed that M2 macrophages were positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation, VCAM-1 secretion, and increased mitochondrial metabolism.
Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies confirmed that ANE enhanced M2 polarization and activated related signaling pathways in the oral buccal tissues of hamsters.
The study concluded that areca nut induces oral carcinogenesis by promoting M2 macrophage differentiation and the secretion of oncogenic cytokines, which critically drive the malignant transformation of oral premalignant cells.
Funding support was provided by NSTC 112-2314-B-037-112-MY3/National Science and Technology Council, Intelligent Drug Systems/Ministry of Education, Smart Biodevices (IDS2B)/Ministry of Education and KMUH109-9R42/Kaohsiung Medical University Chung-Ho Memorial Hospital.
Source: https://pubmed.ncbi.nlm.nih.gov/39160581/
Yuan SF, Chan LP, Nguyen HDH, et al. (2024). “Areca nut-induced metabolic reprogramming and M2 differentiation promote OPMD malignant transformation.” J Exp Clin Cancer Res. 2024 Aug 20;43(1):233. doi: 10.1186/s13046-024-03163-z. PMID: 39160581.
