CD147 overexpression is a prognostic factor and a potential therapeutic target in bladder cancer

Abstract

CD147, also named extracellular matrix metalloproteinase inducer (EMMPRIN), has been shown to be involved in the progression of malignancy by regulating expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). The goal of this study was to evaluate the role of CD147 in the biology of bladder cancer and to determine its potential as a therapeutic target. CD147 protein expression was detected by immunohistochemistry in 108 bladder cancers using a tissue microarray annotated with patient follow-up. In immunohistochemistry, CD147 protein expression was associated with poor prognosis (P<0.001), lymph node status (P<0.001), tumor stage (P=0.003), histologic grade (P=0.011). Multivariate analysis showed that CD147 overexpression was an independent prognostic factor (P=0.019). Infection of T24 bladder cancer cells with an adenovirus that expressed a small interfering RNA (siRNA) against CD147 efficiently inhibited CD147 protein and mRNA expression. This resulted in decreased proliferation, soft agar colony formation, migration, and invasion of T24 cells in vitro. Moreover, downregulation of CD147 reduced secretion of MMP-2 and MMP-9 and expression of VEGF in these cells. Our findings suggest that CD147 overexpression plays an important role in progression of bladder cancer, and CD147 could be a potential target of bladder cancer therapy.