The Expression Of Chemerin In Oral Squamous Cell Carcinoma Promotes Tumor Progression By Regulating The Infiltration And Function Of Neutrophils

Objective:To explore the molecular mechanism of oral squamous cell carcinoma tissue chemerin expression regulating neutrophil infiltration and function to promote the evolution of oral squamous cell carcinoma.Methods:The double staining immunohistochemistry explored the relationship between neutrophil infiltration and chemerin expression,and analyzed the relationship between chemerin expression + neutrophil density and the clinicopathological characteristics and prognosis of patients with oral squamous cell carcinoma(OSCC);flow cytometry Cytometry,Transwell assay,Western blot,enzyme-linked immunosorbent assay and the construction of the lentiviral vector HBLV-h-sh Chem R23 to detect the effect of chemerin on neutrophils chemotaxis.The direct co-culture of tongue squamous cell carcinoma cells and d HL-60 cells and MTT assay were used to detect the effect of chemerin on the killing ability of d HL-60 tumor cells in the co-culture system.Western blot was used to detect the effect of chemerin on the epithelial-mesenchymal transformation related proteins of OSCC via neutrophils.Results:The double staining immunohistochemical results showed that overexpression of chemerin was significantly correlated with increased neutrophil infiltration in oral squamous cell carcinoma tissues(P=0.023),and strong chemerin expression and high neutrophil density was associated with higher clinical stage(P < 0.001),lymph node metastasis(P<0.001)and tumor recurrence(P=0.002);it is not related to the patient’s gender,age,pathological grade,tumor size,and irrelevant(P >0.05).Kaplan – Meier survival analysis showed that patients in the strong chemerin expression + high neutrophil density group had shortened cancer-related overall survival time and disease-free survival time.Transwell results showed that both OSCC cells and recombinant chemerin had a significant chemotactic effect on d HL-60 cells;Chemerin also up-regulated the expression of other neutrophil chemokines IL-17 and CXCL-5 in d HL-60 cells.In addition,the co-culture experiment showed that chemerin weakened the killing effect of d HL-60 cells on OSCC cells(P<0.05).Chemerin may promote epithelial mesenchymal transformation(EMT)of OSCC cells through neutrophils,that is,the expression of N-cadherin and Vimentin is enhanced,while the expression of E-cadherin is decreased.Conclusions:High chemerin expression and high neutrophil density in OSCC are associated with poor clinical outcomes in OSCC patients.Chemerin may attract more neutrophils to the tumor site through its receptor Chem R23 and the up-regulated expression of chemokines IL-17 and CXCL-5.Chemerin weakens the tumor cell killing ability of neutrophils and promotes tumor EMT through neutrophils,thereby promoting tumor evolution and heterogeneity.