Soluble B7-H3 promotes the invasion and metastasis of pancreatic carcinoma cells through the TLR4/NF-κB 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-κB in tumor progression. In the present study, we demonstrate for the first time that sB7-H3 promotes the invasion and metastasis of pancreatic carcinoma cells through the TLR4/NF-κB pathway. In this study, we observed that sB7-H3 was highly expressed in mB7-H3-positive pancreatic carcinoma (PCa) cells. Exogenous sB7-H3 significantly increased NF-κB activity and promoted the migration and invasion of PCa cells. Further studies proved that sB7-H3 first up-regulated TLR4 expression, then activated NF-κB signaling and finally promoted IL-8 and VEGF expression. In contrast, the silencing of TLR4 using a stable short hairpin RNA significantly decreased the sB7-H3-induced activity of NF-κB 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-κB pathway in pancreatic carcinoma cells.
Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei province, People's Republic of China.
Chao
C
Xie
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350000, Fujian province, People's Republic of China.
Danqing
D
Liu
Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei province, People's Republic of China.
Qijun
Q
Chen
Organ Transplantation Center, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu 610072, People's Republic of China.
Chong
C
Yang
Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei province, People's Republic of China.
Bo
B
Wang
Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei province, People's Republic of China.
Heshui
H
Wu
D000818:Animals; D060887:B7 Antigens / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D060887:B7 Antigens; C423237:CD276 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4