新規ファブネクチン受容体抗体LAD-4によるRL♂1リンパ腫の肝臓転移阻害機序
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Gazi MH and Ito M have previously shown that novel monoclonal antibody (mAb) LAD-4 inhibited the binding of RL♂1 lymhoma cells to fibronectin (FN) in vitro and partially those migration to the liver in vivo. In this study, I further examined the ability of LAD-4 to inhibit the RL♂1 liver metastasis and to have a cytopathic effect. Histological examination revealed s.c. inoculation of BALB/c mice with RL♂1 followed i.p. injection of LAD-4 inhibited liver metastasis. Furthermore, flow cytometry (FCM) measurement of number of RL♂1 cells into liver confirmed LAD-4 obviously decreased them. LAD-4 improved survival of mice inoculated intravenously with RL♂1, but was not curative. LAD-4 decreased RL♂1 proliferation in vitro. Adsorbed LAD-4 on the micro-plates downregulated their proliferation under serum-free conditions, but FN did not. Treatment of RL♂1 with LAD-4 for 3h increased Annexin V-positive cells and caspase-3 activation. Moreover, FCM analysis using terminal deoxinucleotidyl transferase (TdT) revealed that 24h treatment of RL ♂1 with LAD-4 induced apoptotic DNA fragmentation. Inhibition of lymphoma cell adhesion to hepatocytic FN have been postulated the mechanism of LAD-4-mediated inhibition of RL♂1 liver metastasis. However, my results suggest that LAD-4 transduces an apoptotic signal through crosslinking of its receptor molecules and this may be another mechanism whereby LAD-4 inhibits RL♂1 liver metastasis. Key words : fibronectin receptor, LAD-4, apoptosis, Annexin V, DNA fragmentation
- 山形大学の論文
- 2004-08-16
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- 新規ファブネクチン受容体抗体LAD-4によるRL♂1リンパ腫の肝臓転移阻害機序