Tumor metastasis is a complex process involving the interaction between tumor cells and endothelial cells in which some adhesion molecules play an important role. It was our aim to investigate the role of the adhesion molecules, alpha v beta 3 and alpha v beta 5 and their ligands, developmental endothelial locus-1 (Del-1) and L1, in tumor cell adhesion to endothelial cells in vitro. In this study, the expression and regulation of alpha v beta 3, alpha v beta 5 and intercellular adhesion molecule -1 on liver sinusoidal endothelial cells and liver cancer endothelial cells (T3A) were analyzed by real-time PCR and fluorescent-activated cell sorter. The expression and regulation of the integrin ligands, Del-1 and L1, in six tumor cell lines were analyzed by real-time PCR and western blot. We found the expressions of alpha v beta 3 and alpha v beta 5 were higher on T3A than that on liver sinusoidal endothelial cells, whereas expression of intercellular adhesion molecule-1 was lower on T3A than that on liver sinusoidal endothelial cells. After 24 h hypoxia, the expressions of alpha v beta 3 and alpha v beta 5 were upregulated on T3A and liver sinusoidal endothelial cells; the expression of intercellular adhesion molecule-1 was increased on liver sinusoidal endothelial cells, but remained unchanged on T3A. Del-1 and L1 expression levels were obviously diverse in various tumor cell lines and differentially modulated after 12 h hypoxia. The adhesion of tumor cells with Del-1 and L1 expression was higher in T3A than that in liver sinusoidal endothelial cells, and was significantly increased under hypoxic conditions. Interestingly, the tumor cell adherence could be inhibited by antibodies against alpha v beta 5 and alpha v beta 5, but not by an antibody against intercellular adhesion molecule-1. The adhesion of tumor cells without Del-1 and L1 expression was also higher on T3A than that on liver sinusoidal endothelial cells, but the adhesion could not be inhibited by antibodies against alpha v beta 5, alpha v beta 5 or intercellular adhesion molecule-1, suggesting that other receptors are involved. In conclusion, alpha v beta 5, alpha v beta 5 and their ligands Del-1 and L1 play an important role in the process of tumor cells moving from the original place.
Background/Aims: The phenotypic and functional characteristics of microvascular endothelial cells derived from human liver cancer (HLCEC) were analyzed in vitro and compared with those of human liver sinusoidal endothelial cells (LSEC). Methods and Results: Flow-cytometric and real-time PCR analysis indicated that expressions of tumor necrosis factor receptor (TNFR) p75, αvβ3 and αvβ5 were increased, while those of TNFR p55 and intercellular-adhesion molecule 1 (ICAM-1) were decreased in HLCEC compared with LSEC. The functional analysis indicated that HLCEC exhibited higher angiogenic ability than LSEC, including proliferation capacity, ability to form capillary-like networks and release of matrix metalloproteinases. In response to tumor necrosis factor, LSEC exhibited a significant dose-dependent cytotoxicity, while HLCEC did not. Moreover, the coagulant and fibrinolytic capacity was increased in HLCEC. In addition, tumor cell adherence was significantly higher on HLCEC than on LSEC, while leukocyte adherence was lower on HLCEC than on LSEC. The cytoadherence of HLCEC was inhibited by antibodies against αvβ3 and αvβ5,and of LSEC by antibodies against ICAM-1. Conclusion: These results indicate that tumor-derived endothelial cells are phenotypically and functionally different from those derived from normal liver tissue. These differences are valuable for understanding tumor angiogenesis and metastasis.
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