This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Indraccolo, S. Articles by Amadori, A. Search for Related Content PubMed PubMed Citation Articles by Indraccolo, S. Articles by Amadori, A.

Gene Transfer in Ovarian Cancer Cells

A Comparison between Retroviral and Lentiviral Vectors¹

IST-Viral and Molecular Oncology Section, Padova, Italy [S. I.]; Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy [W. H., V. T., L. S., E. P., V. T., G. E., L. C-B., A. A.]; Institute of Medical Microbiology, University of Regensburg, Regensburg, Germany [R. W.]; and Department of Molecular and Medical Virology, University of Bochum, Bochum, Germany [K. U.]

Local gene therapy could be a therapeutic option for ovarian carcinoma, a life-threatening malignancy, because of disease containment within the peritoneal cavity in most patients. Lentiviral vectors, which are potentially capable of stable transgene expression, may be useful to vehicle therapeutic molecules requiring long-term production in these tumors. To investigate this concept, we used lentiviral vectors to deliver the enhanced green fluorescent protein (EGFP) gene to ovarian cancer cells. Their efficiency of gene transfer was compared with that of a retroviral vector carrying the same envelope.

In vitro, both vectors infected ovarian cancer cells with comparable efficiency under standard culture conditions; however, the lentiviral vector was much more efficient in transducing growth-arrested cells when compared with the retroviral vector. Gene transfer was fully neutralized by an anti-VSV-G antibody, and in vitro stability was similar.

In vivo, the lentiviral vector delivered the transgene 10-fold more efficiently to ovarian cancer cells growing i.p. in SCID mice, as evaluated by real-time PCR analysis of the tumors. Confocal microscopy analysis of tumor sections showed a dramatic difference at the level of transgene expression, because abundant EGFP⁺ cells were detected only in mice receiving the lentiviral vector. Quantitative analysis by flow cytometry confirmed this and indicated 0.05 and 5.6% EGFP⁺ tumor cells after administration of the retroviral and lentiviral vector, respectively. Injection of ex vivo transduced tumor cells, sorted for EGFP expression, indicated that the lentiviral vector was considerably more resistant to in vivo silencing in comparison with the retroviral vector. Finally, multiple administrations of a murine IFN-₁-lentiviral vector to ovarian carcinoma-bearing mice significantly prolonged the animals’ survival, indicating the therapeutic efficacy of this approach. These findings indicate that lentiviral vectors deserve attention in the design of future gene therapy approaches to ovarian cancer aimed at achieving long-term expression of therapeutic genes.

This article has been cited by other articles:

				L. Persano, L. Moserle, G. Esposito, V. Bronte, V. Barbieri, M. Iafrate, M. P. Gardiman, P. Larghero, U. Pfeffer, E. Naschberger, et al. Interferon-{alpha} counteracts the angiogenic switch and reduces tumor cell proliferation in a spontaneous model of prostatic cancer Carcinogenesis, May 1, 2009; 30(5): 851 - 860. [Abstract] [Full Text] [PDF]

				S. Indraccolo, S. Minuzzo, M. Masiero, I. Pusceddu, L. Persano, L. Moserle, A. Reboldi, E. Favaro, M. Mecarozzi, G. Di Mario, et al. Cross-talk between Tumor and Endothelial Cells Involving the Notch3-Dll4 Interaction Marks Escape from Tumor Dormancy Cancer Res., February 15, 2009; 69(4): 1314 - 1323. [Abstract] [Full Text] [PDF]

				E. Favaro, G. Nardo, L. Persano, M. Masiero, L. Moserle, R. Zamarchi, E. Rossi, G. Esposito, M. Plebani, U. Sattler, et al. Hypoxia Inducible Factor-1{alpha} Inactivation Unveils a Link between Tumor Cell Metabolism and Hypoxia-Induced Cell Death Am. J. Pathol., October 1, 2008; 173(4): 1186 - 1201. [Abstract] [Full Text] [PDF]

				E. Piovan, V. Tosello, S. Indraccolo, M. Masiero, L. Persano, G. Esposito, R. Zamarchi, M. Ponzoni, L. Chieco-Bianchi, R. Dalla-Favera, et al. Differential Regulation of Hypoxia-Induced CXCR4 Triggering during B-Cell Development and Lymphomagenesis Cancer Res., September 15, 2007; 67(18): 8605 - 8614. [Abstract] [Full Text] [PDF]

				R. Hase, M. Miyamoto, H. Uehara, M. Kadoya, Y. Ebihara, Y. Murakami, R. Takahashi, S. Mega, L. Li, T. Shichinohe, et al. Pigment Epithelium-Derived Factor Gene Therapy Inhibits Human Pancreatic Cancer in Mice Clin. Cancer Res., December 15, 2005; 11(24): 8737 - 8744. [Abstract] [Full Text] [PDF]

				E. Kikuchi, S. Menendez, M. Ohori, C. Cordon-Cardo, N. Kasahara, and B. H. Bochner Inhibition of Orthotopic Human Bladder Tumor Growth by Lentiviral Gene Transfer of Endostatin Clin. Cancer Res., March 1, 2004; 10(5): 1835 - 1842. [Abstract] [Full Text] [PDF]

				M. Nour, A. B. Quiambao, M. R. Al-Ubaidi, and M. I. Naash Absence of Functional and Structural Abnormalities Associated with Expression of EGFP in the Retina Invest. Ophthalmol. Vis. Sci., January 1, 2004; 45(1): 15 - 22. [Abstract] [Full Text] [PDF]

				K. Chamoto, T. Tsuji, H. Funamoto, A. Kosaka, J. Matsuzaki, T. Sato, H. Abe, K. Fujio, K. Yamamoto, T. Kitamura, et al. Potentiation of Tumor Eradication by Adoptive Immunotherapy with T-cell Receptor Gene-Transduced T-Helper Type 1 Cells Cancer Res., January 1, 2004; 64(1): 386 - 390. [Abstract] [Full Text] [PDF]

				L. Stievano, V. Tosello, N. Marcato, A. Rosato, A. Sebelin, L. Chieco-Bianchi, and A. Amadori CD8+{alpha}{beta}+ T Cells That Lack Surface CD5 Antigen Expression Are a Major Lymphotactin (XCL1) Source in Peripheral Blood Lymphocytes J. Immunol., November 1, 2003; 171(9): 4528 - 4538. [Abstract] [Full Text] [PDF]