Increased tumor-infiltrating plasmacytoid dendritic cells promote cancer cell proliferation and invasion via TNF-α/NF-κB/CXCR-4 pathway in oral squamous cell carcinoma

Abstract

Background: Tumor-infiltrating immune cells are closely associated with tumor occurrence and progression. The present study explored the potential mechanism of tumor-infiltrating plasmacytoid dendritic cells (pDC) mediating the proliferation and metastasis of cancer cells in oral squamous cell carcinoma (OSCC). Methods: pDC distribution was detected by immunofluorescence and flow cytometry. chemotaxis cytokine receptor-4/7 (CXCR-4/7) expression was detected by quantitative polymerase chain reaction and immunohistochemistry. Cell proliferation and migration were measured by CCK-8, colony formation, wound healing and transwell assay. ELISA and western blotting were used to investigate cytokines secretion and NF-κB pathway activity. Results: Tumor-infiltrating pDC in OSCC was significantly increased and associated with tumor size, lymph node (LN) metastasis (P <0.05). Tumor-infiltrating-pDC-conditioned medium from OSCC patients significantly promoted tumor cell proliferation and invasion, which was at least partly mediated via enhancing the CXCR-4 expression of tumor cell. In addition, the activation of NF-κB pathway played a decisive role in the overexpression of CXCR-4, which was further regulated by pDC-derived TNF-α secretion. Conclusions: Tumor-infiltrating pDC promoted oral cancer proliferation and invasion via activating the TNF-α/NF-κB/CXCR-4 pathway, which may serve as a potential immunological target for the treatment of OSCC in the future.