ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2021; 12(10):3045-3056. doi:10.7150/jca.55580 This issue Cite
Research Paper
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
1. Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
2. Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai, 200011, China.
3. Department of Dentistry, Affiliated Hospital, Weifang Medical University, Weifang, 261031, China.
4. Department of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
5. Department of Stomatology, Shanghai East Hospital, Tongji University. Shanghai 200120, China.
*These authors contributed equally to this work.
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.
Keywords: oral squamous cell carcinoma (OSCC), plasmacytoid dendritic cells (pDCs), lymph node metastasis, nuclear factor-κB (NF-κB), chemotaxis cytokine receptor-4 (CXCR-4)
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