Liver Metastasis Formation Is Defined by AMIGO2 Expression via Adhesion to Hepatic Endothelial Cells in Human Gastric and Colorectal Cancer Cells

Abstract

The adhesion of circulating cancer cells to vascular endothelial cells is an initial and critical step in distant metastases. Amphoterin-induced gene and open reading frame 2 (AMIGO2) was found to regulate tumor cell adhesion to hepatic endothelial cells and act as a driver gene for liver metastasis in mouse cell lines. However, whether the role of AMIGO2 observed in mouse tumor cells can be extrapolated to human cancer cells in vivo has not been verified. In this study, AMIGO2 expression in various human gastric and colorectal cancer cells was found to be closely associated with their adhesion to human hepatic sinusoidal endothelial cells (HHSECs). Constitutive AMIGO2-knockdown clones of human gastric (MKN-45) and colorectal cancer cell lines (DLD-1) were established to examine whether AMIGO2 expression in cancer cells is involved in the adhesion to HHSECs in vitro and the formation of liver metastasis in vivo. All AMIGO2-knockdown cells showed significantly attenuated adhesion to HHSECs. In vivo analysis revealed that intrasplenic inoculation of AMIGO2-knockdown clones could engraft in the spleen but significantly suppressed liver metastasis in nude mice. This study demonstrated that the role of AMIGO2 as a driver gene of liver metastasis in mouse tumor cells can be extrapolated to human cancer cells.

Keywords: AMIGO2; Cell adhesion; Liver endothelial cells; Liver metastasis.