Abstract
Angiogenesis is one of the crucial steps in tumor development and progression, as the formation of a blood vessel network within the tumor enables the tumor to grow and allows tumor cells to enter the blood stream and form distant metastases. Signaling molecules consist mainly of soluble ligands and their receptors on endothelial cells, and the most representative activators are vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF/FGF2). Targeting of angiogenesis activators or the delivery of inhibitors by gene electrotransfer is a promising approach for cancer therapy. Gene electrotransfer is based on electroporation, a physical method, which causes a transient increase in cell membrane permeability due to the application of electric pulses and thus enables the transport of large molecules into cells. Gene electrotransfer was already used to deliver antiangiogenic plasmids or small interfering molecules (siRNA) into cells, targeting different molecular targets involved in angiogenesis, including VEGF pathway, TGF-β and endoglin pathway, integrins, FGF2, and others. Gene electrotransfer of plasmids encoding different antiangiogenic molecules has been proven to be safe, feasible, and effective. Various in vitro and in vivo studies demonstrated its great potential for further research. This approach could easily be implemented into everyday clinical practice. For ensuring safer gene electrotransfer in clinical practice, the use of tissue-specific plasmids, without antibiotic resistance gene, would be preferred.
Similar content being viewed by others
References
Al-Husein B, Abdalla M, Trepte M, Deremer DL, Somanath PR (2012) Antiangiogenic therapy for cancer: an update. Pharmacotherapy 32:1095–1111. doi:10.1002/phar.1147
Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8:604–617. doi:10.1038/nrc2353
Bosnjak M et al (2013) Biological properties of melanoma and endothelial cells after plasmid AMEP gene electrotransfer depend on integrin quantity on cells. J Membr Biol 246:803–819. doi:10.1007/s00232-013-9550-y
Bosnjak M et al (2015) Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma. Gene Ther 22:578–590. doi:10.1038/gt.2015.26
Bossard C, Van den Berghe L, Laurell H, Castano C, Cerutti M, Prats AC, Prats H (2004) Antiangiogenic properties of fibstatin, an extracellular FGF-2-binding polypeptide. Cancer Res 64:7507–7512. doi:10.1158/0008-5472.CAN-04-0287
Brooks PC, Clark RA, Cheresh DA (1994) Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264:569–571
Cemazar M, Jarm T, Sersa G (2010) Cancer electrogene therapy with interleukin-12. Curr Gene Ther 10:300–311
Cichon T, Jamrozy L, Glogowska J, Missol-Kolka E, Szala S (2002) Electrotransfer of gene encoding endostatin into normal and neoplastic mouse tissues: inhibition of primary tumor growth and metastatic spread. Cancer Gene Ther 9:771–777. doi:10.1038/sj.cgt.7700497
Crokart N et al (2013) Potentiation of radiotherapy by a localized antiangiogenic gene therapy. Radiother Oncol 107:252–258. doi:10.1016/j.radonc.2013.03.018
Daugimont L et al (2011) Antitumoral and antimetastatic effect of antiangiogenic plasmids in B16 melanoma: higher efficiency of the recombinant disintegrin domain of ADAM 15. Eur J Pharm Biopharm 78:314–319. doi:10.1016/j.ejpb.2011.02.001
Dolinsek T et al (2013) Multiple delivery of siRNA against endoglin into murine mammary adenocarcinoma prevents angiogenesis and delays tumor growth. PLoS One 8, e58723. doi:10.1371/journal.pone.0058723
Dolinsek T et al (2015a) Endoglin silencing has significant antitumor effect on murine mammary adenocarcinoma mediated by vascular targeted effect. Curr Gene Ther 15:228–244
Dolinsek T, Sersa G, Prosen L, Bosnjak M, Stimac M, Razborsek U, Cemazar M (2015b) Electrotransfer of plasmid DNA encoding an anti-mouse endoglin (CD105) shRNA to B16 melanoma tumors with low and high metastatic potential results in pronounced anti-tumor effects. Cancers 8. doi:10.3390/cancers8010003
Figg WDFMJ (2008) Angiogenesis an integrative approach from science to medicine. Springer. http://worldcat.org. http://public.eblib.com/EBLPublic/PublicView.do?ptiID=371390
Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–286. doi:10.1038/nrd2115
Li S, Zhang L, Torrero M, Cannon M, Barret R (2005) Administration route- and immune cell activation-dependent tumor eradication by IL12 electrotransfer. Mol Ther 12:942–949. doi:10.1016/j.ymthe.2005.03.037
Lucas ML, Heller L, Coppola D, Heller R (2002) IL-12 plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16.F10 melanoma. Mol Ther 5:668–675. doi:10.1006/mthe.2002.0601
Martel-Renoir D et al (2003) Coelectrotransfer to skeletal muscle of three plasmids coding for antiangiogenic factors and regulatory factors of the tetracycline-inducible system: tightly regulated expression, inhibition of transplanted tumor growth, and antimetastatic effect. Mol Ther 8:425–433
Nassiri F et al (2011) Endoglin (CD105): a review of its role in angiogenesis and tumor diagnosis, progression and therapy. Anticancer Res 31:2283–2290
Prosen L, Markelc B, Dolinsek T, Music B, Cemazar M, Sersa G (2014) Mcam silencing with RNA interference using magnetofection has antitumor effect in murine melanoma. Mol Ther Nucleic Acids 3, e205. doi:10.1038/mtna.2014.56
Rosen LS, Gordon MS, Robert F, Matei DE (2014) Endoglin for targeted cancer treatment. Curr Oncol Rep 16:365. doi:10.1007/s11912-013-0365-x
Shibata MA, Morimoto J, Shibata E, Otsuki Y (2008) Combination therapy with short interfering RNA vectors against VEGF-C and VEGF-A suppresses lymph node and lung metastasis in a mouse immunocompetent mammary cancer model. Cancer Gene Ther 15:776–786. doi:10.1038/cgt.2008.43
Spanggaard I et al (2013) Gene electrotransfer of plasmid antiangiogenic metargidin peptide (AMEP) in disseminated melanoma: safety and efficacy results of a phase I first-in-man study. Hum Gene Ther Clin Dev 24:99–107. doi:10.1089/humc.2012.240
Stimac M, Dolinsek T, Lampreht U, Cemazar M, Sersa G (2015) Gene electrotransfer of plasmid with tissue specific promoter encoding shRNA against endoglin exerts antitumor efficacy against murine TS/A tumors by vascular targeted effects. PLoS One 10, e0124913. doi:10.1371/journal.pone.0124913
Stimac M, Kamensek U, Cemazar M, Kranjc S, Coer A, Sersa G (2016) Tumor radiosensitization by gene therapy against endoglin. Cancer Gene Ther 23:214–220. doi:10.1038/cgt.2016.20
Tesic N et al (2015) Endoglin (CD105) silencing mediated by shRNA under the control of endothelin-1 promoter for targeted gene therapy of melanoma. Mol Ther Nucleic Acids 4, e239. doi:10.1038/mtna.2015.12
Vader P et al (2011) Examining the role of Rac1 in tumor angiogenesis and growth: a clinically relevant RNAi-mediated approach. Angiogenesis 14:457–466. doi:10.1007/s10456-011-9229-x
Verrax J et al (2011) Delivery of soluble VEGF receptor 1 (sFlt1) by gene electrotransfer as a new antiangiogenic cancer therapy. Mol Pharm 8:701–708. doi:10.1021/mp100268t
Yadav L, Puri N, Rastogi V, Satpute P, Sharma V (2015) Tumour angiogenesis and angiogenic inhibitors: a review. J Clin Diagn Res 9:XE01–XE05. doi:10.7860/JCDR/2015/12016.6135
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2016 Springer International Publishing AG
About this entry
Cite this entry
Cemazar, M., Dolinsek, T., Bosnjak, M., Sersa, G. (2016). Antiangiogenic Gene Therapy. In: Miklavcic, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-26779-1_51-1
Download citation
DOI: https://doi.org/10.1007/978-3-319-26779-1_51-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Online ISBN: 978-3-319-26779-1
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences