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Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy

Cancer Gene Therapy volume 8, pages 491–496 (2001)Cite this article

Abstract

The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatment reduced melanoma growth by 50% to 90% compared to that occurring in control animals treated with liposome-coated plasmid carrying the lacZ gene or in untreated controls. The growth of both locally injected and controlateral uninjected tumors in mice bearing two melanoma grafts was significantly suppressed after intratumoral treatment. Tumor growth inhibition was also observed in mice treated by intraperitoneal delivery, suggesting that angiostatin gene therapy acts through a systemic effect. Both melanoma growth suppression and delay in the onset of tumor growth were observed in treated mice. PCR performed on tumors and normal tissues showed that the lipofected DNA was present in tissues from treated mice, and angiostatin expression was demonstrated by RT-PCR. Histopathological analysis of melanoma nodules revealed an increase in apoptotic cells and a reduction in vessel density in tumors from treated mice. Our results suggest that systemic, liposome-mediated administration of genes coding for antiangiogenic factors represents a promising strategy for melanoma treatment in humans. Cancer Gene Therapy (2001) 8, 491–496

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Acknowledgements

We thank Dr. Licia Rivoltini and Dr. Andrea Anichini (INT, Milan) for providing Me501 and 1402P human melanoma cell lines. The technical assistance of Dario Strina and Lucia Susani is acknowledged. We thank Prof. R. Dulbecco and Prof. L. Rossi Bernardi for continuous support during the study. The financial support of AIRC to M.G.S. and of the Progetto Finalizzato Biotecnologie to P.V. are gratefully acknowledged. This is manuscript no. 49 of the Genoma 2000/ITBA Project funded by CARIPLO. The financial support of the CARIPLO Foundation to Istituto Nazionale Tumori is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy

    Monica Rodolfo, Marco Asioli & Giorgio Parmiani

  2. Department of Human Genome and Multifactorial Disease, CNR-ITBA, Milan, Italy

    Enrica Mira Catò, Sabina Soldati, Roberta Ceruti, Paolo Vezzoni & Maria Grazia Sacco

  3. Istituto di Anatomia Patologica Veterinaria e Patologia Aviare, University of Milan, Milan, Italy

    Sabina Soldati, Roberta Ceruti & Eugenio Scanziani

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  1. Monica Rodolfo
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Correspondence to Monica Rodolfo.

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Rodolfo, M., Catò, E., Soldati, S. et al. Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy. Cancer Gene Ther 8, 491–496 (2001). https://doi.org/10.1038/sj.cgt.7700331

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