IL-7, acting via IL-7 receptor (IL-7R), plays an important role in tumor progression. Elevated IL-7 expression has been reported to be observed in prostate cancer tissues and closely associated with poor prognosis. However, the biological functions of IL-7 and its receptor in prostate cancer cell invasiveness remain unclear. In our study, we found that the expressions of IL-7 and IL-7R were both upregulated in prostate cancer cells. IL-7 dose-dependently promoted the invasion and migration of prostate cancer cells, whereas knockdown of IL-7R attenuated the effect of IL-7. Further, IL-7/IL-7R axis induced the activation of AKT and NF-κB, whereas blocking of AKT suppressed IL-7-mediated NF-κB activity. Moreover, IL-7/IL-7R axis increased MMP-3 and MMP-7 expression of prostate cancer cells, whereas inhibition of NF-κB as well as MMPs activity suppressed IL-7-mediated cell invasion and migration. Together, these data identify IL-7/IL-7R axis to be involved in prostate cancer cell invasion and migration, probably via activating AKT/NF-κB pathway and upregulating MMP-3 and MMP-7 expression. Therefore, blocking IL-7/IL-7R axis may provide a potential therapeutic strategy to treat prostate cancer.
International immunopharmacology. 2016 Sep 06 [Epub ahead of print]
Hu Qu, Zihao Zou, Zhaojun Pan, Tianwei Zhang, Nan Deng, Guoxi Chen, Zhongyang Wang
Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, PR China., Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, PR China., Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, PR China. Electronic address: .