IEO model: A novel concept describing the complete metastatic process in the liver microenvironment.

Metastasis is a characteristic behavior of malignant tumor cells. It is determined by the mutual interaction between primary tumor cells and the state of the microenvironment at sites of metastasis, particularly the liver, bone, lungs and brain. In the present review, a novel pattern is defined and termed the IEO model (prI-, prE- and pOst-metastatic niche), for the hepatic metastatic microenvironment which characterizes the complete metastatic process. In the IEO model, the components of the hepatic metastatic niche, including the extracellular matrix, hepatocytes, mesenchymal cells, Kupffer cells, hepatic sinusoidal endothelial cells, hepatic stellate cells and immunocytes are continually remodelled by tumor cells to form various microenvironments during different stages of hepatic metastasis. The IEO model explains the plasticity of the hepatic microenvironment and provides novel insights into the role of different stages of the metastatic niche. This novel concept may provide a basis for advances in theoretical cancer research and for improvements in the complete course management of malignant tumors.