EpCAM expression in breast cancer cells is associated with enhanced bone metastasis formation

Epithelial cell adhesion molecule (EpCAM) has been implicated in multiple cellular functions including cell adhesion. EpCAM has also recently been identified as a marker for cancer stem cells (CSCs). Here, we examined the roles of EpCAM in the development of bone metastasis of breast cancer by using well‐characterized animal models. Morphological and real‐time reverse transcriptase‐polymerase chain reaction data showed that the EpCAM‐negative and ‐positive (EpCAM neg and EpCAM pos ) cell populations isolated from breast cancer cell lines exhibited mesenchymal and epithelial phenotypes, respectively. Flow cytometric analysis revealed that EpCAM pos , but not EpCAM neg , cells possessed self‐renewal and differentiation potentials. Tumorsphere formation in suspension cultures and tumorigenicity in the orthotopic mammary fat pad of mice were significantly greater in EpCAM pos cells than in EpCAM neg cells. The development of bone metastases induced by an intracardiac injection was markedly increased in mice inoculated with EpCAM pos cells. Furthermore, intracardiac inoculations of parental cells demonstrated that the EpCAM pos population in cancer cells that colonized in bone was significantly higher than that in parental cells. However, stable transduction of EpCAM into EpCAM neg cells failed to reproduce the phenotypes of EpCAM pos cells. These results suggest that the expression of EpCAM in breast cancer cells is associated with CSC‐like phenotypes, which contribute to the promotion of bone metastases by enhancing tumorigenicity. Our results also support the possibility that the epithelial phenotypes of EpCAM‐expressing cells confer advantageous properties for the development of bone metastases, at least after entering the circulation, while EpCAM is likely not solely responsible for the phenotypes of EpCAM pos cells.