Interactions between colon cancer cells and hepatocytes in rats in relation to metastasis

Abstract Adhesion of cancer cells to endothelium is considered an essential step in metastasis. However, we have shown in a previous study that when rat colon cancer cells are administered to the vena portae, they get stuck mechanically in liver sinusoids. Then, endothelial cells retract rapidly and cancer cells bind to hepatocytes. We investigated the molecular nature of these interactions between colon cancer cells and hepatocytes. Cancer cells in coculture with hepatocytes became rapidly activated with distinct morphological changes. Cancer cells formed long cytoplasmic protrusions towards hepatocytes in their close vicinity and these protrusions attached to microvilli of hepatocytes. Then, adhering membrane areas were formed by both cell types. Integrin subunits αv, α6 and β1 but not αL, β2, β3 and CD44 and CD44v6 were expressed on the cancer cells. In conclusion, colon cancer cells show an active behaviour to bind to hepatocytes, likely involving the integrin subunits av, a6 and B1, indicating that early events in colon cancer metastasis in liver are distinctly different than assumed thus far.