Tumor metastasis is a complicated pathophysilogy procedure including tumor cells moving from the place of origin and subsequent adhesion at a secondary site. These procedures involves cellular adhesion molecules mediated interaction among tumor cells, endothelial cells and platelets.Objective To analyze the expression and regulation of adhesion molecules with their ligands in endothelial cells and tumor cells; To compare the adhesion of tumor cells in cancer-derived endothelial cells and normal endothelial cells and analyze the role of these adhesion molecules in tumor adhesion; To investigate the effect of platelet on tumor cell-endothelial cell adhesion.Methods The expression and regulation ofαvβ3,αvβ5 and ICAM-1 in liver sinusoidal endothelial cells (LSEC) and liver cancer endothelial cells (T3A) were analyzed by Real-time PCR and fluorescent activated cell sorter (FACS) respectively. The expression and regulation of Del-1 and L1 in six tumor cell lines were analyzed by Real-time PCR and Western Blot respectively. The adhesion of tumor cells in LSEC and T3A was measured by a fluorescence plate reader after co-culture of tumor cells labeled with fluorescent dye and analyzed with antibodies against different adhesion molecules. The effect of platelet on tumor cell-endothelial cell adhesion was investigated and the role of adhesion molecules in this procedure were analyzed.Results FACS indicated that the expression ofαvβ3 andαvβ5 were higher in T3A than that in LSEC, while expression of ICAM-1 was lower in T3A than that in LSEC. These results were further demonstrated by Real-time PCR in transcription levels. By Real-time PCR and FACS, the expression ofαvβ3 andαvβ5 was found to be up-regulated in T3A and LSEC after hypoxia for 24 hours, and although the expression of ICAM-1 was increased in LSEC, that in T3A was unaltered. The expression of Del-1 and L1 molecules were different obviously in various tumor cell lines. The expression of Del-1 and L1 was positive in BEL7402, while was negative in HOS. The expression of Del-1 was up-regulated BEL7402 cell lines, but was unchanged in HOS cell lines after hypoxia for 12 hours.The adhesion of tumor cells was higher in T3A than that in LSEC, and the difference has statistic significance between the two groups. The tumor cell adherence was significantly increased after hypoxia of endothelial cells or hypoxia of tumor cells. The tumor cell adherence could be inhibited by antibodies againstαvβ3 andαvβ5, but not by antibody against ICAM-1. Interestingly, the adhesion of HOS tumor cells without Del -1 and L1 expression was high in T3A and LSEC, but couldn't be inhibited by antibodies againstαvβ3 ,αvβ5 and ICAM-1. These data suggest that there are other mechanisms besidesαvβ3,αvβ5 and ICAM-1 in the adhesion of tumor cell-endothelial cells.BEL7402 cell lines and human lung endothelial cells were all adhered to platelets. The adhesion of BEL7402 cell lines in endothelial cells was significantly increased by platelets, and the tumor cells adhesion mediated by platelet could be inhibted by antibody against gpⅡb/Ⅲa.Conclusion The adhesion molecules,αvβ3 andαvβ5 and their ligands play an important role in mediating tumor cells moving from the original place; while the platelet promoted tumor cells planting into the metastatic place. |