Current views concerning the influences of murine hepatic endothelial adhesive and cytotoxic properties on interactions between metastatic tumor cells and the liver

This review summarizes the current findings of adhesive and cytotoxic endothelial-tumor cell interactions in the liver, the inducibility, zonal distribution and sinusoidal structural influences on the hepatic endothelial regulatory functions, and the effects of these functions on the formation of liver cancer metastases. New insights into the traditional cancer metastatic cascade are also discussed.The formation of a metastatic tumor in the secondary organ is the result of dissemination of a primary cancer cell, survival in the circulation, passing through the vascular bed in the distant organ and cancer cell proliferation [1-4]. Cancer metastasis is known to be an inefficient process, which reflects the fact that most of the intravascular cancer cells are killed within blood vessels or lymphatic channels [5,6]. Metastasis is accomplished in a step-wise or metachronous fashion [6,7]. More recent studies using mouse and rat models and in vivo video microscopy have demonstrated that the initial steps of the haematogenous metastatic process, from cancer cells entering the bloodstream to extravasating into secondary organs, are completed with remarkable efficiency [8,9]. The inefficiency is more associated with the subsequent steps involving cell division and formation of micrometastases by extravasated cancer cells in the secondary site [7,8,10]. In contrast, other studies have indicated that the majority of disseminating tumor cells die rapidly in the blood circulation and can not pass the first capillary bed they encounter [8,11-13]. With the metastatic cascade being well-outlined in the literature, the specific underlying mechanisms of tumor cell loss in the circulation and secondary organs, and the determinant factors for metastases formation still remain to be fully elucidated [3,10,14].Recent in vivo and in vitro experimental evidence from various laboratories strongly suggests that, during the interactions between an organ microvascular bed and intravascular tum