Targeting of breast metastases using a viral gene vector with tumour-selective transcription.

2.50
Hdl Handle:
http://hdl.handle.net/10147/206352
Title:
Targeting of breast metastases using a viral gene vector with tumour-selective transcription.
Authors:
Rajendran, Simon; Collins, Sara; van Pijkeren, Jan P; O'Hanlon, Deirdre; O'Sullivan, Gerald C; Tangney, Mark
Affiliation:
Cork Cancer Research Centre, Mercy University Hospital, Cork, Ireland.
Citation:
Anticancer Res. 2011 May;31(5):1627-35.
Journal:
Anticancer research
Issue Date:
31-Jan-2012
URI:
http://hdl.handle.net/10147/206352
PubMed ID:
21617219
Abstract:
BACKGROUND: Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression. MATERIALS AND METHODS: We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse models of breast cancer and in patient samples, using bioluminescent imaging and flow cytometric analysis. RESULTS: Higher transgene expression levels were observed in subcutaneous MCF-7 tumours relative to normal tissue (muscle) using the CXCR4 promoter, unlike a ubiquitously expressing Cytomegalovirus promoter construct, with preferential AAVCXCR4 expression in epithelial tumour and CXCR4-positive cells. Transgene expression following intravenously administered AAVCXCR4 in a model of liver metastasis was detected specifically in livers of tumour bearing mice. Ex vivo analysis using patient samples also demonstrated higher AAVCXCR4 expression in tumour compared with normal liver tissue. CONCLUSION: This study demonstrates for the first time, the potential for systemic administration of AAV2 vector for tumour-selective gene therapy.
Language:
eng
MeSH:
Adenocarcinoma/genetics/pathology/*therapy; Animals; Breast Neoplasms/genetics/*pathology/*therapy; Dependovirus/*genetics; Female; Flow Cytometry; *Gene Therapy; Gene Transfer Techniques; Genetic Vectors/*administration & dosage; Humans; Liver Neoplasms/genetics/secondary/*therapy; Mice; Mice, Nude; Promoter Regions, Genetic; Receptors, CXCR4/genetics; Transcription, Genetic; Transduction, Genetic; Tumor Cells, Cultured
ISSN:
1791-7530 (Electronic); 0250-7005 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorRajendran, Simonen_GB
dc.contributor.authorCollins, Saraen_GB
dc.contributor.authorvan Pijkeren, Jan Pen_GB
dc.contributor.authorO'Hanlon, Deirdreen_GB
dc.contributor.authorO'Sullivan, Gerald Cen_GB
dc.contributor.authorTangney, Marken_GB
dc.date.accessioned2012-01-31T16:40:01Z-
dc.date.available2012-01-31T16:40:01Z-
dc.date.issued2012-01-31T16:40:01Z-
dc.identifier.citationAnticancer Res. 2011 May;31(5):1627-35.en_GB
dc.identifier.issn1791-7530 (Electronic)en_GB
dc.identifier.issn0250-7005 (Linking)en_GB
dc.identifier.pmid21617219en_GB
dc.identifier.urihttp://hdl.handle.net/10147/206352-
dc.description.abstractBACKGROUND: Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression. MATERIALS AND METHODS: We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse models of breast cancer and in patient samples, using bioluminescent imaging and flow cytometric analysis. RESULTS: Higher transgene expression levels were observed in subcutaneous MCF-7 tumours relative to normal tissue (muscle) using the CXCR4 promoter, unlike a ubiquitously expressing Cytomegalovirus promoter construct, with preferential AAVCXCR4 expression in epithelial tumour and CXCR4-positive cells. Transgene expression following intravenously administered AAVCXCR4 in a model of liver metastasis was detected specifically in livers of tumour bearing mice. Ex vivo analysis using patient samples also demonstrated higher AAVCXCR4 expression in tumour compared with normal liver tissue. CONCLUSION: This study demonstrates for the first time, the potential for systemic administration of AAV2 vector for tumour-selective gene therapy.en_GB
dc.language.isoengen_GB
dc.subject.meshAdenocarcinoma/genetics/pathology/*therapyen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBreast Neoplasms/genetics/*pathology/*therapyen_GB
dc.subject.meshDependovirus/*geneticsen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFlow Cytometryen_GB
dc.subject.mesh*Gene Therapyen_GB
dc.subject.meshGene Transfer Techniquesen_GB
dc.subject.meshGenetic Vectors/*administration & dosageen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLiver Neoplasms/genetics/secondary/*therapyen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Nudeen_GB
dc.subject.meshPromoter Regions, Geneticen_GB
dc.subject.meshReceptors, CXCR4/geneticsen_GB
dc.subject.meshTranscription, Geneticen_GB
dc.subject.meshTransduction, Geneticen_GB
dc.subject.meshTumor Cells, Cultureden_GB
dc.titleTargeting of breast metastases using a viral gene vector with tumour-selective transcription.en_GB
dc.contributor.departmentCork Cancer Research Centre, Mercy University Hospital, Cork, Ireland.en_GB
dc.identifier.journalAnticancer researchen_GB
dc.description.provinceMunster-

Related articles on PubMed

All Items in Lenus,the Irish health repository are protected by copyright, with all rights reserved, unless otherwise indicated.