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.
IntroductionCholangiocarcinoma is one of the most aggressive malignant tumors associated with local tissue invasion and a high rate of metastasis and is one of the most common causes of cancer death in Thailand (1). Three-year survival rates of 35-50% are achieved only in a subset of patients who have negative histological margins at the time of surgery (2-5). Palliative therapeutic approaches, including percutaneous and endoscopic biliary drainage, have generally been used for these patients because there is no effective chemotherapeutic treatment for cholangiocarcinoma. Therefore, identification of the molecules involved in cholangiocarcinoma cell progression is crucial for the development of novel drug treatments for this disease.CD24 is a small, heavily glycosylated mucin-like glycosylphosphatidylinositol (GPI)-linked cell surface protein that serves as a ligand for P-selectin, an adhesion receptor on activated endothelial cells and platelets (6). CD24 can be detected in granulocytes, pre-B-cells and keratinocytes (7) and its expression in non-small cell lung cancer, ovarian cancer and hepatocellular carcinoma is associated with poor prognoses (8,9). However, only limited studies have been published on CD24 expression in cholangiocarcinoma (10,11) and there are no data on the mechanism of CD24 involvement in cholangiocarcinoma cell progression. In the present study, we investigated the clinicopathological significance of CD24 expression in human cholangiocarcinoma samples. We also determined the cellular function of CD24 in cholangiocarcinoma cells by isolating CD24 + and CD24 -cells from the RMCCA1 cholangiocarcinoma cell line and assessing cell pro...