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A tricistronic retroviral vector expressing natural antiangiogenic factors inhibits angiogenesis in vitro, but is not able to block tumor progression in vivo

Gene Therapy volume 9, pages 297–302 (2002)Cite this article

Abstract

Angiogenesis, the formation of new blood vessels out of pre-existing capillaries, is essential for tumor progression. Many factors have been identified that are able to inhibit angiogenesis. Here, we report the construction of a tricistronic retroviral vector encoding two inhibitors of angiogenesis expressed in mammals: the N-terminal fragment of rat prolactin (16KrPRL) and a secreted form of human platelet factor 4 (sPF4). When transduced by this retroviral vector, a rat glioblastoma cell line loses its ability of promoting endothelial cell locomotion, the initial step of angiogenesis, and the formation of an endothelial cell tube network. In spite of this encouraging in vitro result, however, the anti-angiogenic vector cannot block glioblastoma progression in animal models. These results suggest that therapeutic strategies aiming to block tumor progression through the inhibition of tumor-associated angiogenesis, should not only provide large numbers of angiogenesis inhibitors, but also target the angiogenic factors produced by tumor cells. Moreover, the data described herein may confirm recent findings from other groups which indicate that in order to successfully counteract tumor progression, drugs inhibiting new blood vessel formation should be employed in combination with traditional anti-tumor strategies, such as chemotherapy or radiotherapy.

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Acknowledgements

We thank Dr AF Parlow and the National Hormone and Pituitary Program, NIDDK, for providing rat prolactin and specific antisera for this study. We are grateful to Dr Roberto Sorge, from the Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, Rome, Italy, for the valuable help in Kaplan–Meier data elaboration. We also thank T Delli Castelli and G Bonelli for excellent technical assistance. This study was funded in part by grants from the Italian Ministry of Instruction, University and Scientific Research (MIUR) to MGF and to GB, from the Italian Ministry of Health to MGF, and from the Italian Consiglio Nazionale delle Ricerche (CNR) to MGF and to SAC.

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Authors and Affiliations

  1. Department of Experimental Medicine and Biochemical Sciences, University of Rome, ‘Tor Vergata’, Rome, Italy

    SA Ciafrè, G Barillari, L Bongiorno-Borbone, F Wannenes & MG Farace

  2. Department of Internal Medicine, University of Rome, ‘Tor Vergata’, Rome, Italy

    F Wannenes

  3. Departamento de Biologìa Molecular-Centro de Biologìa Molecular Severo Ochoa, Universidad Autònoma de Madrid, Cantoblanco, Madrid, Spain

    M Izquierdo

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  1. SA Ciafrè
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  2. G Barillari
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  4. F Wannenes
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Ciafrè, S., Barillari, G., Bongiorno-Borbone, L. et al. A tricistronic retroviral vector expressing natural antiangiogenic factors inhibits angiogenesis in vitro, but is not able to block tumor progression in vivo. Gene Ther 9, 297–302 (2002). https://doi.org/10.1038/sj.gt.3301652

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