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Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide

Oncogene volume 21, pages 7700–7709 (2002)Cite this article

Abstract

Ewing sarcoma is the second most common bone tumor in childhood. Despite aggressive chemotherapy and radiotherapy strategies, the prognosis of patients with metastatic disease remains poor. We have recently reported that Ewing tumor cell proliferation was strongly inhibited by IFN-β and to a lesser degree by IFN-α. Moreover, under IFN-β treatment, some cell lines undergo apoptosis. Since the possibility of using IFNs for Ewing tumor treatments may be of interest, we have evaluated the efficacy of Hu-IFNs in a nude mice model of Ewing tumor xenografts. The results reported here show that human type I IFNs, Hu-IFN-α and Hu-IFN-β impaired tumor xenograft take and displayed an anti-growth effect toward established xenografts. Furthermore, we have also shown that combined therapy with Hu-IFNs and ifosfamide (IFO), an alkylating agent widely used in high-dose chemotherapy of Ewing tumors, results in a strong antitumor effect. Pathological analysis showed that Hu-IFN-α/IFO and Hu-IFN-β/IFO were characterized by a dramatic decrease in the mitotic index and marked necrosis, as well as extensive fibrosis associated with numerous calcifications. To our knowledge, this is the first demonstration of a potential antitumor effect of human type I IFNs and IFO on Ewing tumors, providing a rational foundation for a promising therapeutic approach to Ewing sarcoma.

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Acknowledgements

The authors would like to thank BioSidus (Buenos Aires, Argentina) for the gift of human Hu-IFN-α-2b (Bioferon®), and Ares Serono (Basel, Switzerland) for the gift of human Hu-IFN-β 1a (REBIF®). We thank Professor Gilbert Lenoir (Dept Pédiatrie, Hôpital Necker-Enfants-Malades, Paris, France) for providing the Ewing cells used in this study. We are grateful to Vincent Bordier, Claire Chevalier and Christophe Alberti for technical assistance for animal experimentation, and Catherine Silvestri for cell culture. This work was supported by grants from the Institut National Scientifique et de la Recherche Medicale (INSERM), the Association pour le Recherche Contre le Cancer (ARC) and BioSidus (Argentina).

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Authors and Affiliations

  1. INSERM U365, Institut Curie, Section Recherche 26, rue d'Ulm, 75 248 , Paris, Cedex 05, France

    Josiane Sancéau & Juana Wietzerbin

  2. CNRS-UMR 147, Institut Curie, Section Recherche 26, rue d'Ulm, 75 248, Paris, Cedex 05, France

    Marie-France Poupon

  3. INSERM U509, Institut Curie, Section Recherche 26, rue d'Ulm, 75 248, Paris, Cedex 05, France

    Olivier Delattre

  4. Department of Pathology, MD, Institut Curie, Section Médicale, 26 rue d'Ulm, 75 248, Paris, Cedex 05, France

    Xavier Sastre-Garau

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  1. Josiane Sancéau
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Correspondence to Juana Wietzerbin.

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Sancéau, J., Poupon, MF., Delattre, O. et al. Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide. Oncogene 21, 7700–7709 (2002). https://doi.org/10.1038/sj.onc.1205881

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