Expression of Cadherin-17 Promotes Metastasis in a Highly Bone Marrow Metastatic Murine Breast Cancer Model

Abstract

We previously established 4T1E/M3 highly bone marrow metastatic mouse breast cancer cells through in vivo selection of 4T1 cells. But while the incidence of bone marrow metastasis of 4T1E/M3 cells was high (80%) when injected intravenously to mice, it was rather low (20%) when injected subcutaneously. Therefore, using 4T1E/M3 cells, we carried out further in vitro and in vivo selection steps to establish FP10SC2 cells, which show a very high incidence of metastasis to lungs (100%) and spines (85%) after subcutaneous injection into mice. qRT-PCR and western bolt analysis revealed that cadherin-17 gene and protein expression were higher in FP10SC2 cells than in parental 4T1E/M3 cells. In addition, immunostaining revealed the presence of cadherin-17 at sites of bone marrow and lung metastasis after subcutaneous injection of FP10SC2 cells into mice. Suppressing cadherin-17 expression in FP10SC2 cells using RNAi dramatically decreased the cells' anchorage-independent growth and migration in vitro and their metastasis to lung and bone marrow in vivo. These findings suggest that cadherin-17 plays a crucial role in mediating breast cancer metastasis to bone marrow.