Downregulation of VAP‐1 in OSCC suppresses tumor growth and metastasis via NF‐κB/IL‐8 signaling and reduces neutrophil infiltration
Background Vascular adhesion protein‐1 (VAP‐1) is believed to play a role in inflammation. Studies have suggested that VAP‐1‐mediated activation of inflammation is dependent on NF‐κB, leading to secretion of the interleukin (IL)‐8; however, no reports have addressed the association between VAP‐1 and...
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Veröffentlicht in: | Journal of oral pathology & medicine 2022-04, Vol.51 (4), p.332-341 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Background
Vascular adhesion protein‐1 (VAP‐1) is believed to play a role in inflammation. Studies have suggested that VAP‐1‐mediated activation of inflammation is dependent on NF‐κB, leading to secretion of the interleukin (IL)‐8; however, no reports have addressed the association between VAP‐1 and NF‐κB/IL‐8 signaling in oral squamous cell carcinoma (OSCC). This study aimed to investigate the role of VAP‐1 in OSCC and further explore whether VAP‐1 is involved in the regulation of neutrophil infiltration in the tumor microenvironment (TME).
Methods
Immunochemistry staining was used to observe VAP‐1 expression. CCK‐8 and Transwell assays were used to measure cell proliferation, migration, and invasion. OSCC xenograft mouse models were used for in vivo verification of the VAP‐1 function. The expression of NF‐κB and IL‐8 were determined by qRT‐PCR and western blot. ELISA for IL‐8 was also conducted. The relationship between VAP‐1 expression and neutrophil infiltration was analyzed by immunofluorescence.
Results
VAP‐1 was overexpressed in human OSCC tissues. Downregulation of VAP‐1 suppressed OSCC cells proliferation, migration, and invasion in vitro and inhibited tumor proliferation and metastasis in vivo. Additionally, downregulation of VAP‐1 inhibited NF‐κB/IL‐8 signaling in vitro and in vivo. VAP‐1 expression was positively correlated with neutrophil infiltration in human OSCC tissues. Moreover, blocking VAP‐1 decreased neutrophil infiltration by reducing IL‐8 production.
Conclusions
VAP‐1 downregulation in OSCC suppresses tumor growth and metastasis by inhibiting NF‐κB/IL‐8 signaling and reducing neutrophil infiltration in the TME, suggesting that VAP‐1 may be a potential therapeutic target for OSCC. |
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ISSN: | 0904-2512 1600-0714 |
DOI: | 10.1111/jop.13285 |