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Antitumor effect of B16 melanoma cells genetically modified with the angiogenesis inhibitor RNasin

Cancer Gene Therapy volume 8, pages 278–284 (2001)Cite this article

Abstract

The growth of new blood vessels is an essential condition for the development of tumors with a diameter greater than 1–2 mm and also for their metastatic dissemination. RNasin, the placental ribonuclease inhibitor, is known to have antiangiogenic activity through the inhibition of angiogenin and basic fibroblast growth factor. Nevertheless, the administration of the recombinant form of a protein poses several limitations; as a result, we have studied the antitumor effect of RNasin in a murine gene therapy model. RNasin cDNA was subcloned into the pcDNA3 expression vector, and the resulting recombinant plasmid was used to transfect the B16 murine melanoma cell line. An RNasin inverted construction was used as control. Mice intravenously injected with clones expressing RNasin showed a significant inhibition of tumor metastatic progression with respect to control groups (P<.001) and survived longer (P<.001). Tissue sections from RNasin-expressing cell tumors showed a lower number of blood vessels when compared to tissue sections from mice lungs that had been inoculated with control cell lines. The results of these experiments show that the genetic modification of tumor cells with RNasin cDNA yields a significant antitumor effect, and suggest that this effect is at least partially the result of angiogenesis inhibition. Cancer Gene Therapy (2001) 8, 278–284

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Acknowledgements

The authors are grateful to D. T. Curiel and the Internal Forum of Gene Therapy Center (University of Alabama at Birmingham, UT) for their valuable criticism of the manuscript. The authors also thank Alejo Sempere (Department of Pathology, University of Valencia) for performance of immunohistochemistry. This work has been partially supported by Generalitat Valenciana (GV-C-VS-20-114-96) and IMTEFA/1999/52 projects.

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Authors and Affiliations

  1. Servicio de Dermatología, Instituto Valenciano de Oncología, Universitat de València, Valencia, Spain

    Rafael Botella-Estrada, Onofre Sanmartín & Carlos Guillén

  2. Departamento de Farmacología, Facultad de Medicina y Odontología, Universitat de València, Valencia, Spain

    Gema Malet, Fernando Revert, Francisco Dasí, Antonio Crespo & Salvador F Aliño

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  1. Rafael Botella-Estrada
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Correspondence to Rafael Botella-Estrada.

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Botella-Estrada, R., Malet, G., Revert, F. et al. Antitumor effect of B16 melanoma cells genetically modified with the angiogenesis inhibitor RNasin. Cancer Gene Ther 8, 278–284 (2001). https://doi.org/10.1038/sj.cgt.7700302

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