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 investigate the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in metastatic lymph nodes from gastrointestinal cancer. METHODS: Metastatic lymph nodes from gastrointestinal cancer were detected for RCAS1 by immunohistochemical staining and mRNA in situ hybridization. RESULTS: A total of 102 metastatic lymph nodes from bile duct, gastric, colon and pancreatic cancer were investigated for RCAS1 expression. The immunoreactivity of RCAS1 was identified in 100% of metastatic lymph nodes. Both local and distant metastatic lymph nodes showed RCAS1 expression. On the contrary, specimens of non-cancerous lymph nodes were negative for RCAS1. The result of mRNA in situ hybridization was also confirmed by the finding of immunohistochemical staining. RCAS1 mRNA was detected in all tumor cells that metastasized to lymph nodes. CONCLUSION: All metastatic lymph nodes express RCAS1 in tumor cells at both mRNA levels, and RCAS1 that should be used as a complementary factor for identification of metastatic lymph nodes from gastrointestinal cancers.
