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dc.contributor.authorHashimi, SM
dc.contributor.authorYu, S
dc.contributor.authorAlqurashi, N
dc.contributor.authorIpe, DS
dc.contributor.authorWei, MQ
dc.date.accessioned2017-05-03T15:30:09Z
dc.date.available2017-05-03T15:30:09Z
dc.date.issued2013
dc.date.modified2014-01-15T21:47:52Z
dc.identifier.issn1019-6439
dc.identifier.doi10.3892/ijo.2013.1881
dc.identifier.urihttp://hdl.handle.net/10072/55628
dc.description.abstractImmunotoxins are engineered chimeric proteins that consist of a fragment of a toxin fused to a modified antibody or growth factor capable of targeting specific cells. Furthermore, these proteins can be targeted to receptors that are commonly overexpressed on cancer cells. The majority of immunotoxins function by binding to cells, translocating into the cytosol and inhibiting protein synthesis. In this study, the expression of claudin-4 (CLDN4) in various cancer cells was analysed as a potential target for immunotoxins. To target CLDN4-expressing cancer cells, the c-terminal CLDN4-binding domain of Clostridium perfringens enterotoxin (CPE) was fused to the Pseudomonas aeruginosa exotoxin A (ETA) domain to create an immunotoxin (CPE-ETA'). Subsequently, the capacity of such an immunotoxin in suppressing the proliferation of CLDN4-positive cancer cells was investigated. We report that head and neck squamous carcinoma cells (HN5) have an elevated CLDN4 expression compared to the other cell lines tested. Our findings further demonstrate that CPE-ETA' is highly potent against MCF-7 breast [50% inhibitory concentration (IC50) 9.8 ng/ml] and HN5 head/neck (IC50 8.8 ng/ml) cancer cell lines, while it has no cytotoxic effects on HeLa cells (CLDN4-negative). The immunotoxin was subsequently expressed in the tumour colonising oncolytic strain, Clostridium ghonii. Most importantly, the strictly anaerobic Clostridium ghonii was able to overexpress and secrete a functional CPE-ETA' fusion protein. Our findings open the possibility of the targeted delivery of the immunotoxin locally to tumour sites at a high concentration using strictly anaerobic Clostridium ghonii for the treatment of CLDN4-positive cancer cells.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent1266253 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherSpandidos Publications
dc.publisher.placeGreece
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1911
dc.relation.ispartofpageto1918
dc.relation.ispartofissue6
dc.relation.ispartofjournalInternational Journal of Oncology
dc.relation.ispartofvolume42
dc.rights.retentionY
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchCancer therapy (excl. chemotherapy and radiation therapy)
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321104
dc.titleImmunotoxin-mediated targeting of claudin-4 inhibits the proliferation of cancer cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Dentistry and Oral Health
gro.rights.copyright© 2013 Spandidos Publications. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2013
gro.hasfulltextFull Text
gro.griffith.authorWei, Ming Q.


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