دورية أكاديمية
أعرض في EDS

Targeted induction of apoptosis in glioblastoma multiforme cells by an MRP3-specific TRAIL fusion protein in vitro.

التفاصيل البيبلوغرافية
العنوان: Targeted induction of apoptosis in glioblastoma multiforme cells by an MRP3-specific TRAIL fusion protein in vitro.
المؤلفون: Wang LH; Department of Biochemistry and Molecular Biology, Second Military Medical University, Xiangyin Road No. 800, Shanghai, 200433, China., Ni CW, Lin YZ, Yin L, Jiang CB, Lv CT, Le Y, Lang Y, Zhao CY, Yang K, Jiao BH, Yin J
المصدر: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine [Tumour Biol] 2014 Feb; Vol. 35 (2), pp. 1157-68. Date of Electronic Publication: 2013 Nov 26.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: IOS Press Country of Publication: Netherlands NLM ID: 8409922 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1423-0380 (Electronic) Linking ISSN: 10104283 NLM ISO Abbreviation: Tumour Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2021- : Amsterdam, The Netherlands : IOS Press
Original Publication: Tokyo, Japan : Saikon Pub. Co., c1984-
مواضيع طبية MeSH: Brain Neoplasms/*genetics , Glioblastoma/*genetics , Multidrug Resistance-Associated Proteins/*immunology , Recombinant Fusion Proteins/*genetics , TNF-Related Apoptosis-Inducing Ligand/*immunology, Antigens, Surface/genetics ; Antigens, Surface/immunology ; Apoptosis/genetics ; Brain Neoplasms/pathology ; Brain Neoplasms/therapy ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Glioblastoma/pathology ; Glioblastoma/therapy ; Humans ; Jurkat Cells ; Multidrug Resistance-Associated Proteins/genetics ; Multidrug Resistance-Associated Proteins/therapeutic use ; Recombinant Fusion Proteins/immunology ; Recombinant Fusion Proteins/therapeutic use ; Single-Chain Antibodies/genetics ; Single-Chain Antibodies/immunology ; TNF-Related Apoptosis-Inducing Ligand/genetics ; TNF-Related Apoptosis-Inducing Ligand/therapeutic use
مستخلص: Single-chain Fv fragments (scFvs) consist of the variable heavy-chain (VH) and variable light-chain (VL) domains, which are the smallest immunoglobulin fragments containing the whole antigen-binding site. Human soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) proves to acquire a potent pro-apoptotic activity only after selective binding to a predefined tumor cell surface antigen and has no off-target effects towards normal cells. Glioblastoma multiforme (GBM) is the most frequent and aggressive type of brain tumor and overexpresses human multidrug resistance protein 3 (MRP3). In this study, we designed a novel fusion protein, termed scFvM58-sTRAIL, in which the MRP3-specific scFv antibody M58 was genetically fused to the N-terminus of human soluble TRAIL (sTRAIL). The recombinant scFvM58-sTRAIL fusion protein, expressed in Escherichia coli, was purified by chromatography and tested for cytotoxicity. scFvM58-sTRAIL showed a significant apoptosis-inducing activity towards MRP3-positive GBM cells in vitro. The pro-apoptotic activity of scFvM58-sTRAIL towards GBM cells was strongly inhibited in the presence of the parental scFvM58 antibody, suggesting that cytotoxic activity is MRP3-restricted. In a control experiment with MRP3-negative Jurkat cells, scFvM58-sTRAIL did not induce apparent apoptosis. In addition, through target antigen-restricted binding, scFvM58-sTRAIL was capable of activating not only TRAIL-R1 but also TRAIL-R2. In conclusion, our results suggest that fusion protein scFvM58-sTRAIL with specificity for MRP3 is a highly selective therapeutic agent and may provide an alternative therapy for human GBM.
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المشرفين على المادة: 0 (Antigens, Surface)
0 (Multidrug Resistance-Associated Proteins)
0 (Recombinant Fusion Proteins)
0 (Single-Chain Antibodies)
0 (TNF-Related Apoptosis-Inducing Ligand)
0 (TNFSF10 protein, human)
1YV0492L5Z (multidrug resistance-associated protein 3)
تواريخ الأحداث: Date Created: 20131126 Date Completed: 20140428 Latest Revision: 20211021
رمز التحديث: 20231215
DOI: 10.1007/s13277-013-1155-7
PMID: 24272336
قاعدة البيانات: MEDLINE
الوصف
تدمد:1423-0380
DOI:10.1007/s13277-013-1155-7