ABSTRACT
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.
Subject(s)
Bile Duct Neoplasms/immunology , Bile Ducts, Intrahepatic/pathology , CD24 Antigen/biosynthesis , Cholangiocarcinoma/immunology , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , CD24 Antigen/genetics , Cell Adhesion/immunology , Cell Growth Processes/immunology , Cell Line, Tumor , Cell Movement/immunology , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Disease Progression , Drug Resistance, Neoplasm , Humans , Lymphatic Metastasis , Matrix Metalloproteinase 7/metabolism , Matrix Metalloproteinase 9/metabolism , Multivariate Analysis , Neoplasm Invasiveness , Paraffin Embedding , PrognosisABSTRACT
AIM: To determine the role of CD133 in cholangiocarcinoma progression. METHODS: CD133 protein expression was evaluated by immunohistochemistry in 34 cholangiocarcinoma specimens. In addition, proliferation, chemoresistance and invasive properties of CD133-enriched (CD133(+)) and CD133-depleted (CD133(-)) RMCCA1 cholangiocarcinoma cells were studied and compared. RESULTS: Strong CD133 expression was observed in 67.6% (23/34) of the cholangiocarcinoma specimens. Strong expression of CD133 was significantly associated with nodal metastasis (P = 0.009) and positive surgical margin status (P = 0.011). In the in vitro study, both the CD133(+) and CD133(-) cells had similar proliferation abilities and resistance to chemotherapeutic drugs. However, the CD133(+) cells had a higher invasive ability compared with CD133(-) cells. CONCLUSION: CD133+ cells play an important role in the invasiveness of cholangiocarcinoma. Targeting of the CD133+ cells may be a useful approach to improve treatment against cholangiocarcinoma.
