Low-dose TNF-α promotes angiogenesis of oral squamous cell carcinoma cells via TNFR2/Akt/mTOR axis

Objectives: To assess the role of TNF-alpha/TNFR2 axis on promoting angiogenesis in oral squamous cell carcinoma (OSCC) cells and uncover the underlying mechanisms. Materials and Methods: The expression of TNFR2 and CD31 in OSCC tissues was examined; gene expression relationship between TNF-alpha/TNFR2 and angiogenic markers or signaling molecules was analyzed; the expression of angiogenic markers, signaling molecules, TNFR1, and TNFR2 in TNF-alpha-stimulated OSCC cells treated with or without TNFR2 neutralizing antibody (TNFR2 Nab) were assessed; the concentration of angiogenic markers in the supernatant of OSCC cells was detected; conditioned mediums of OSCC cells treated with TNF-alpha or TNF-alpha + TNFR2 Nab were applied to human umbilical vein endothelial cells (HUVECs), followed by tube formation and cell migration assays. Results: Significantly elevated expression of TNFR2 and CD31 in OSCC tissues was observed. A positive gene expression correlation was identified between TNF-alpha/TNFR2 and angiogenic markers or signaling molecules. TNFR2 Nab inhibited the effects of TNF-alpha on enhancing the expression of angiogenic factors and TNFR2, the phosphorylation of the Akt/mTOR signaling pathway, HUVECs migration, and tube formation. Conclusions: TNFR2 Nab counteracts the effect of TNF-alpha on OSCC cells through the TNFR2/Akt/mTOR axis, indicating that blocking TNFR2 might be a promising strategy against cancer.

Automated summary

The study assessed the role of the TNF-alpha/TNFR2 axis in promoting angiogenesis in oral squamous cell carcinoma (OSCC) cells and uncovered the mechanisms involved. The results showed that TNFR2 neutralizing antibody (TNFR2 Nab) could counteract the effects of TNF-alpha on OSCC cells through the TNFR2/Akt/mTOR axis, suggesting that blocking TNFR2 might be a promising strategy against cancer.