Department of Urology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, 110001, Shenyang City, Liaoning, China.
Med Oncol. 2011 Dec;28(4):1363-72. doi: 10.1007/s12032-010-9582-4. Epub 2010 May 28.
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.
CD147,也称为细胞外基质金属蛋白酶诱导因子(EMMPRIN),通过调节血管内皮生长因子(VEGF)和基质金属蛋白酶(MMPs)的表达,被证明参与了恶性肿瘤的进展。本研究的目的是评估 CD147 在膀胱癌生物学中的作用,并确定其作为治疗靶点的潜力。使用组织微阵列(带有患者随访注释)通过免疫组织化学检测 108 例膀胱癌中的 CD147 蛋白表达。在免疫组织化学中,CD147 蛋白表达与不良预后(P<0.001)、淋巴结状态(P<0.001)、肿瘤分期(P=0.003)、组织学分级(P=0.011)相关。多变量分析显示,CD147 过表达是独立的预后因素(P=0.019)。用表达针对 CD147 的小干扰 RNA(siRNA)的腺病毒感染 T24 膀胱癌细胞,可有效抑制 CD147 蛋白和 mRNA 的表达。这导致 T24 细胞体外增殖、软琼脂集落形成、迁移和侵袭能力降低。此外,下调 CD147 可减少 MMP-2 和 MMP-9 的分泌以及这些细胞中 VEGF 的表达。我们的研究结果表明,CD147 过表达在膀胱癌的进展中起着重要作用,CD147 可能是膀胱癌治疗的潜在靶点。