中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells

文献类型:期刊论文

作者Yi B1,2; Zhang M1,2; Schwartz-Albiez R3; Cao Y[*]1
刊名INTERNATIONAL JOURNAL OF ONCOLOGY
出版日期2011
卷号38期号:6页码:1565-1573
关键词CD176 Thomsen-Friedenreich antigen leukemia apoptosis signaling pathway
通讯作者caoy@mail.kiz.ac.cn
合作状况其它
英文摘要CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate structure. In a previous study, we observed that the anti-CD176 antibody can induce the apoptosis of CD176-positive leukemic cells. In this study, we investigated the mechanisms of apoptosis induced by the CD176 antibody. We found that CD95 (FAS, APO-1) and the death receptor 4 (DR4) (TRAIL-R1) are co-expressed with CD176 on the surface of defined leukemic cells as observed by confocal microscopy and flow cytometry analyses. Furthermore, CD95, CD45, CD43 and DR4 are carrier proteins of CD176 in hematopoietic cells recognized by means of sandwich solid-phase enzyme linked irnmunosorbent assay and co-immunoprecipitation. As shown by microarray analysis, 20 genes which are directly related to the execution, induction or positive regulation of apoptosis, were up-regulated after CD176 antibody treatment of the KG1 cell line. Nine differentially expressed genes observed in the microarray analysis were verified by quantitative real-time polymerase chain reaction in the KG1 and MT4 cell lines. Six genes (DAXX, CASP3, CHUK, RIPK2, NFKBIA and DFFA) out of these nine are involved in five apoptotic pathways: The CD95 signaling pathway, the DR3 and DR4/5 death receptor pathway, caspase cascade in apoptosis, the mitochondrial signaling pathway, and apoptotic DNA fragmentation and tissue homeostasis. Thus, we hypothesized that the CD176 antibody binds to the CD176 carbohydrate structure present on apoptosis-associated glycoproteins, such as CD95 and DR4 at the cellular surface, which activates apoptotic pathways, and consequently results in the apoptosis of CD176-positive cells. CD176 is expressed at the surface of human leukemic cells, but is almost absent in normal and benign adult human tissues. Thus, CD176 could be a promising target for anti-tumor therapy based on the induction of tumor-specific apoptosis.
资助信息This study was financially supported by grants from the Yunnan Province Science and Technology Department (2008CCO15), the Chinese Academy of Sciences (KSCX2- YW-R-196), and the National Natural Science Foundation of China (No. 81072563).
收录类别SCI
语种英语
公开日期2011-08-11
源URL[http://159.226.149.42:8088/handle/353002/6645]  
专题昆明动物研究所_分子病理学
昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位1.Laboratory of Molecular and Experimental Pathology, Key Laboratory of Animal Models and Human Disease Mechanism of CAS and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiaochang Donglu, Kunming, Yunnan 650223
2.Graduate University of the Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049, P.R. China
3.Translational Immunology Unit, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany
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Yi B,Zhang M,Schwartz-Albiez R,et al. Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2011,38(6):1565-1573.
APA Yi B,Zhang M,Schwartz-Albiez R,&Cao Y[*].(2011).Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells.INTERNATIONAL JOURNAL OF ONCOLOGY,38(6),1565-1573.
MLA Yi B,et al."Mechanisms of the apoptosis induced by CD176 antibody in human leukemic cells".INTERNATIONAL JOURNAL OF ONCOLOGY 38.6(2011):1565-1573.

入库方式: OAI收割

来源:昆明动物研究所

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