Department of Molecular Medicine, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Int J Oncol. 2011 Oct;39(4):873-81. doi: 10.3892/ijo.2011.1088. Epub 2011 Jun 17.
Cholangiocarcinoma is frequently found to invade local tissues and metastasize to distal organs. We investigated the expression of CD24 in cholangiocarcinoma samples and its prognostic significance. In addition, the cellular function of CD24 was studied in the RMCCA1 cholangiocarcinoma cell line. High CD24 expression significantly correlated with lymph node metastasis and positive surgical margins in cholangiocarcinoma patients. Univariate and multivariate analyses further demonstrated that CD24 expression was significantly associated with the overall survival of these patients (p=0.007 and p=0.040, respectively). For in vitro studies, the magnetic-activated cell sorting (MACS) system was used to isolate CD24+ and CD24- cell populations from RMCCA1 cells. CD24+ RMCCA1 cells had increased chemoresistance, adhesion (p=0.004), motility (p<0.001), migration (p<0.001) and invasion (p<0.001) capabilities when compared to CD24- cells. The matrix metalloproteinase (MMP)-7 was significantly elevated in CD24+ RMCCA1 cells (p=0.01). We found that inhibition of CD24 using siRNA silencing significantly decreased the invasive capacity of RMCCA1 cells. Both clinical and in vitro studies suggest that expression of CD24 is associated with cholangiocarcinoma disease progression. CD24 may thus serve as a new target for directed molecular therapy of cholangiocarcinoma.
胆管癌常发现侵犯局部组织并转移至远处器官。我们研究了胆管癌样本中 CD24 的表达及其预后意义。此外,还在 RMCCA1 胆管癌细胞系中研究了 CD24 的细胞功能。高 CD24 表达与胆管癌患者的淋巴结转移和阳性手术切缘显著相关。单因素和多因素分析进一步表明,CD24 表达与这些患者的总生存率显著相关(p=0.007 和 p=0.040)。对于体外研究,使用磁激活细胞分选(MACS)系统从 RMCCA1 细胞中分离 CD24+和 CD24-细胞群。与 CD24-细胞相比,CD24+ RMCCA1 细胞具有更高的化疗耐药性、粘附性(p=0.004)、迁移性(p<0.001)、迁移性(p<0.001)和侵袭性(p<0.001)。CD24+ RMCCA1 细胞中基质金属蛋白酶(MMP)-7 显著升高(p=0.01)。我们发现,使用 siRNA 沉默抑制 CD24 表达可显著降低 RMCCA1 细胞的侵袭能力。临床和体外研究均表明,CD24 的表达与胆管癌的疾病进展有关。因此,CD24 可能成为胆管癌靶向分子治疗的新靶点。