Interleukin-32 stimulates osteosarcoma cell invasion and motility via AKT pathway-mediated MMP-13 expression

Abstract

As a pro-inflammatory cytokine, interleukin-32 (IL-32) is reported to play an important role in tumor development and progression. However, its effects on the invasion and motility of osteosarcoma cells remain elusive. The aim of the present study was to determine the molecular mechanisms of IL-32 in osteosarcoma cells using RT-PCR and western blot analysis. The results showed that IL-32 stimulation dose-dependently promoted the invasion and motility of osteosarcoma cells. Knockdown of endogenous IL-32 by siRNA inhibited osteosarcoma cell invasion and motility. Moreover, IL-32 induced the activation of AKT in a time-dependent manner. IL-32 stimulationwas also capable of increasing the expression and secretion of matrix metalloproteinase (MMP)-13, which is involved in tumor invasion and metastasis. In addition, blockade of AKT activation suppressed IL-32-mediated invasion, motility and MMP-13 upregulation in osteosarcoma cells. Taken together, our results suggest that IL-32 stimulation promotes the invasion and motility of osteosarcoma cells, possibly via the activation of AKT and the upregulation of MMP-13 expression. Thus, IL-32 may serve as a marker for diagnosis, as well as for the treatment of osteosarcoma.