美罗华
酸性鞘磷脂酶
脂筏
癌症研究
木筏
脂质微区
鞘磷脂
淋巴瘤
化学
医学
免疫学
内科学
生物化学
膜
受体
有机化学
共聚物
聚合物
作者
Christine Bezombes,Solène Grazide,Céline Garret,Claire Fabre,Anne Quillet‐Mary,Sabina Müller,Jean‐Pierre Jaffrézou,Guy Laurent
出处
期刊:Blood
[American Society of Hematology]
日期:2004-04-22
卷期号:104 (4): 1166-1173
被引量:118
标识
DOI:10.1182/blood-2004-01-0277
摘要
Rituximab is a chimeric human immunoglobulin G1 (IgG1) anti-CD20 monoclonal antibody with significant activity against CD20 malignant B cells. Rituximab is currently used with success in the treatment of B-cell‐derived lymphoid neoplasias either alone or in combination with chemotherapy. However, the predominant mechanism by which rituximab exerts its antitumor properties in vivo remains unknown. In the present study, we demonstrate that in Daudi and RL B-lymphoma cells, rituximab (without cross-linking) used at the saturating dose of 10 g/mL induced moderate accumulation in G1 phase, growth inhibition, and significant loss in clonogenic potential. However, in these cells, rituximab induced no apoptosis. Furthermore, we observed that treatment with rituximab resulted in a rapid and transient increase in acid-sphingomyelinase (A-SMase) activity and concomitant cellular ceramide (CER) generation in raft microdomains. We also observed that rituximab-treated cells externalized both A-SMase and CER that colocalized with the CD20 receptor. Finally, we present evidence that rituximab-induced growth inhibition may be mediated through a CER-triggered signaling pathway, leading to the induction of cell cycle‐dependent kinase inhibitors such as p27(Kip1) through a mitogenactivated protein kinase (MAPK)‐dependent mechanism. (Blood. 2004;104: 1166-1173)
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