Distinct cellular responses induced by saporin and a transferrin-saporin conjugate in two different human glioblastoma cell lines
Distinct cellular responses induced by saporin and a transferrin-saporin conjugate in two different human glioblastoma cell lines
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DOI：
10.1002/jcp.22805
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发表时间：
2012-03-01
影响因子：
5.6
通讯作者：
Ippoliti, R.
中科院分区：
文献类型：
--
作者：
Cimini, A.;Mei, S.;Ippoliti, R.
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性脑肿瘤，诊断后的中位生存期为1218个月。GBM通常在切除后12个月内复发，预后差。因此，迫切需要靶向和杀死GBM细胞的新的治疗策略。肿瘤细胞相对于正常脑细胞的显著差异使得胶质母细胞瘤成为选择性靶向治疗的良好候选者。最近的实验策略集中在过表达的细胞表面受体。靶向毒素代表了一类由有效蛋白毒素和载体配体组成的新的选择性分子。针对胶质母细胞瘤的靶向毒素方法正在I期和II期临床试验中进行研究，其中使用了几种免疫毒素（IT）/配体毒素，如IL 4-铜绿假单胞菌外毒素A（IL 4-PE，NBI-3001）、与PE 38融合的肿瘤生长因子、较短的PE变体、（TGF）α-TP-38、IL 13-PE 38和转铁蛋白-C白喉毒素突变体（Tf-CRM 107）。在这项工作中，我们研究了植物核糖体失活皂草素及其嵌合体转铁蛋白皂草素对两种不同的GBM细胞系的影响。这里获得的数据表明，细胞增殖受到毒素处理的影响，但使用不同的机制，直接与活性或非活性p53的存在。提出了这些替代细胞内途径的模型。J.细胞。227：939951，2012。(C)2011 Wiley Periodicals，Inc.
Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults, with a median survival of similar to 1218 months post-diagnosis. GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are urgently needed. The marked difference of tumour cells with respect to normal brain cells renders glioblastoma a good candidate for selective targeted therapies. Recent experimental strategies focus on over expressed cell surface receptors. Targeted toxins represent a new class of selective molecules composed by a potent protein toxin and a carrier ligand. Targeted toxins approaches against glioblastoma were under investigation in phase I and II clinical trials with several immunotoxins (IT)/ligand toxins such as IL4-Pseudomonas aeruginosa exotoxin A (IL4-PE, NBI-3001), tumour growth factor fused to PE38, a shorter PE variant, (TGF)alpha-TP-38, IL13-PE38, and a transferrin-C diphtheriae toxin mutant (Tf-CRM107). In this work, we studied the effects of the plant ribosome-inactivating saporin and of its chimera transferrinsaporin against two different GBM cell lines. The data obtained here indicate that cell proliferation is affected by the toxin treatments but that different mechanisms are used, directly linked to the presence of an active or inactive p53. A model is proposed for these alternative intracellular pathways. J. Cell. Physiol. 227: 939951, 2012. (C) 2011 Wiley Periodicals, Inc.