کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10752526 | 1050328 | 2015 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Type II anti-CD20 mAb-induced lysosome mediated cell death is mediated through a ceramide-dependent pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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![عکس صفحه اول مقاله: Type II anti-CD20 mAb-induced lysosome mediated cell death is mediated through a ceramide-dependent pathway Type II anti-CD20 mAb-induced lysosome mediated cell death is mediated through a ceramide-dependent pathway](/preview/png/10752526.png)
چکیده انگلیسی
In the past decade, monoclonal antibodies (mAbs) have revolutionized the treatment of non-Hodgkin lymphomas (NHLs). Although Fc-dependent mechanisms of mAb-mediated tumor clearance have been extensively studied, the ability of mAbs to directly evoke programmed cell death (PCD) and the underlying mechanisms involved remain unclear. It is well established that type II anti-CD20 mAb (Tositumomab) potently evoked PCD through a caspases-independent, lysosome-mediated process, which is related to homotypic adhesion (HA) in NHL cell lines. Herein, we reveal that the induction of ceramide generation by anti-CD20 mAbs directly correlates with their ability to induce PCD. The inhibition of ceramide abrogated Tositumomab-induced PCD indicating that ceramide is required for the execution of cell death. Further experimental results revealed that ceramide was generated downstream of mAb-induced HA and upstream of lysosome leakage. These findings provide further insights into a previously unrecognized role for ceramide generation in mediating PCD evoked by type II anti-CD20 mAbs in Burkitt's lymphoma cells. This newly characterized cell death pathway may potentially be exploited to eliminate malignant cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 457, Issue 4, 20 February 2015, Pages 572-577
Journal: Biochemical and Biophysical Research Communications - Volume 457, Issue 4, 20 February 2015, Pages 572-577
نویسندگان
Hua Ren, Chengwei Zhang, Liwei Su, Xin Bi, Chao Wang, Liang Wang, Bo Wu,