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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Enhanced tumour cell nuclear targeting in a tumour progression model

Authors: Michael S Nastasie, Helmut Thissen, David A Jans, Kylie M Wagstaff

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

There is an urgent need for new approaches to deliver bioactive molecules to cancer cells efficiently and specifically.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
Enhanced tumour cell nuclear targeting in a tumour progression model
Authors
Michael S Nastasie
Helmut Thissen
David A Jans
Kylie M Wagstaff
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1045-z

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