Enhanced tumour cell nuclear targeting in a tumour progression model.
Enhanced tumour cell nuclear targeting in a tumour progression model.
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DOI：
10.1186/s12885-015-1045-z
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发表时间：
2015-02-21
期刊：
影响因子：
3.8
通讯作者：
Wagstaff KM
中科院分区：
文献类型：
--
作者：
Nastasie MS;Thissen H;Jans DA;Wagstaff KM
迫切需要新的方法来有效、特异地将生物活性分子递送至癌细胞。在这里，我们将鸡贫血病毒凋亡蛋白的癌细胞核靶向模块与核心组蛋白 H2B 和 H3 融合，并将其用于转染、蛋白质转导和 DNA 结合测定。我们发现，在转染的同基因人骨肉瘤和乳腺肿瘤进展模型中，与正常细胞相比，这些蛋白质随后在肿瘤中的核积累量高出 2-3 倍。这代表了在肿瘤进展模型中 Apoptin 增强的核靶向性及其在异源蛋白质环境中的功能的首次演示。令人兴奋的是，我们发现组蛋白的先天转导能力可以与 Apoptin 核靶向模块结合使用，使骨肉瘤癌细胞核的蛋白质递送量比同基因正常细胞核的蛋白质递送量高出 13 倍。这是细胞穿透蛋白对癌细胞特异性的第一份报告，对于未来使用蛋白质转导作为基因/药物递送载体具有重要意义，特别是在开发高度特异性和有效的抗癌药物方面。本文的在线版本 (doi:10.1186/s12885-015-1045-z) 包含补充材料，可供授权用户使用。
There is an urgent need for new approaches to deliver bioactive molecules to cancer cells efficiently and specifically. Here we fuse the cancer cell nuclear targeting module of the Chicken Anaemia Virus Apoptin protein to the core histones H2B and H3 and utilise them in transfection, protein transduction and DNA binding assays. We found subsequent nuclear accumulation of these proteins to be 2–3 fold higher in tumour compared to normal cells in transfected isogenic human osteosarcoma and breast tumour progression models. This represents the first demonstration of enhanced nuclear targeting by Apoptin in a tumour progression model, and its functionality in a heterologous protein context. Excitingly, we found that the innate transduction ability of histones could be exploited in combination with the Apoptin nuclear targeting module to effect an overall 13-fold higher delivery of protein to osteosarcoma cancer cell nuclei compared to their isogenic normal counterparts. This is the first report of cancer-cell specificity by a cell penetrating protein, with important implications for the use of protein transduction as a vehicle for gene/drug delivery in the future, and in particular in the development of highly specific and effective anti-cancer agents. The online version of this article (doi:10.1186/s12885-015-1045-z) contains supplementary material, which is available to authorized users.
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影响因子：
5.4
作者：
Nguyen, Nang L.;Loveland, Amy N.;Gibson, Wade
通讯作者：
Gibson, Wade
DOI：
10.1073/pnas.1137864100
发表时间：
2003-06-10
影响因子：
11.1
作者：
Harley, VR;Layfield, S;Jans, DA
通讯作者：
Jans, DA
影响因子：
56.9
作者：
HUANG, HJS;YEE, JK;LEE, WH
通讯作者：
LEE, WH
DOI：
10.1016/0304-419x(93)90021-4
发表时间：
1993-05-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
GOODRICH, DW;LEE, WH
通讯作者：
LEE, WH
影响因子：
3.5
作者：
Leliveld, SR;Dame, RT;Abrahams, JP
通讯作者：
Abrahams, JP