Soluble B7-H3 Promotes The Invasion And Metastasis Of Pancreatic Carcinoma Cells Through The TLR4/NF-?B Pathway

Many studies have demonstrated a relationship between soluble B7-H3(sB7-H3)and the poor prognosis of patients with malignant tumors,and increasing evidence has shown a connection between sB7-H3 and NF-?B in tumor progression.In the present study,we demonstrate for the frst time that sB7-H3 promotes the invasion and metastasis of pancreatic carcinoma cells through the TLR4/NF-?B pathway.In this study,we observed that sB7-H3 was highly expressed in mB7-H3-positive pancreatic carcinoma(PCa)cells.Exogenous sB7-H3 signifcantly increased NF-?B activity and promoted the migration and invasion of PCa cells.Further studies proved that sB7-H3 frst up-regulated TLR4 expression,then activated NF-?B signaling and fnally promoted IL-8 and VEGF expression.In contrast,the silencing of TLR4 using a stable short hairpin RNA signifcantly decreased the sB7-H3-induced activity of NF-?B and the expression of IL-8 and VEGF in PCa cells.In vivo animal experiments further demonstrated that TLR4-knock-down tumor cells displayed a decreased ability to metastasize compared with the control tumor cells after being induced by sB7-H3.Collectively,these results demonstrate that sB7-H3 promotes invasion and metastasis through the TLR4/NF-?B pathway in pancreatic carcinoma cells.