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Evaluation of the Glypican 3 promoter for transcriptional targeting of hepatocellular carcinoma

journal contribution
posted on 26.03.2019, 00:00 by B Dhungel, S Andrzejewski, A Jayachandran, R Shrestha, Charmaine Ramlogan-SteelCharmaine Ramlogan-Steel, CJ Layton, Jason SteelJason Steel
© 2018 Macmillan Publishers Ltd., part of Springer Nature. Hepatocellular carcinoma (HCC) is a major health problem as evidenced by its increasing incidence and high morbidity and mortality rates. Most patients with HCC have underlying liver disease and dysfunction which limits the current therapeutic options. Treatments that spare the liver and destroy the HCC are needed. Targeting transcriptional differences between HCC and liver cells may provide this therapeutic window. In this study, we examine the potential of the Glypican 3 (GPC3) promoter as a targeting strategy. GPC3 is an oncofetal protein belonging to the proteoglycan family which is normally only expressed during fetal development. However, in HCC, the expression of this protein is reactivated. Here, we show that GPC3 is expressed primarily in HCC and not in normal liver lines. We show that the GPC3 promoter can be used to drive expression of significantly more luciferase and eYFP in HCC cell lines compared to normal liver cells. Further, we show that vectors containing cytosine deaminase (CD) under GPC3 promotor control induced significantly more killing of HCC cell lines after treatment with 5-FC compared to normal liver cell lines. These data suggest that transcriptionally targeted delivery of transgene in HCC cells can be achieved using the GPC3 promoter and this targeting strategy produces limited toxicity to normal liver cells.

Funding

Other

History

Volume

25

Issue

2

Start Page

115

End Page

128

Number of Pages

13

eISSN

1476-5462

ISSN

0969-7128

Publisher

Nature Publishing Group, UK

Peer Reviewed

Yes

Open Access

No

Acceptance Date

27/12/2017

External Author Affiliations

Greenslopes Private Hospital, Qld; University of Queensland

Era Eligible

Yes

Journal

Gene Therapy

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