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Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing's sarcoma cells

Cancer Gene Therapy volume 9, pages 296–307 (2002)Cite this article

Abstract

The insulin-like growth factor I receptor (IGF-IR) plays an essential role in the establishment and maintenance of transformed phenotype of Ewing's sarcoma (ES) cells, and interference with the IGF-IR pathways by a neutralizing antibody causes reversal of the malignant potential of this neoplasm. In this paper, we stably transfected an IGF-IR antisense mRNA expression plasmid in an ES cell line to determine the effectiveness of antisense strategies against the in vitro and in vivo growth of ES cells. Doxorubicin sensitivity of TC-71 cells expressing antisense targeted to IGF-IR mRNA was also examined. Cells carrying antisense IGF-IR had a reduced expression of the receptor, a modest decrease in cell proliferation, a significant increase in anoikis-induced apoptosis, and a severely reduced ability to form colonies in soft agar. Moreover, TC/AS cells showed a marked reduction in their motility. In vivo, when cells carrying antisense IGF-IR were injected subcutaneously in nude mice, tumor formation was delayed and survival increased. Metastatic ability of ES cells was also significantly reduced. Furthermore, TC/AS clones showed a significantly higher sensitivity to doxorubicin — a major drug in the treatment of ES. These results indicate that inhibiting IGF-IR by antisense strategies may be relevant to the clinical treatment of ES patients by reducing the malignant potential of these cells and enhancing the effectiveness of chemotherapy.

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Acknowledgements

This work was supported by grants from the Italian Association for Cancer Research, the Italian Ministry for University and Research, and the Rizzoli Institute. VC is the recipient of a Fellowship from the Italian Foundation for Cancer Research. We thank Renato Baserga (Kimmel Cancer Center, Thomas Jefferson University) for kindly providing us with the plasmid expressing antisense sequences to IGF-IR RNA.

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Authors and Affiliations

  1. Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy

    Katia Scotlandi, Cecilia Maini, Maria Cristina Manara, Stefania Benini, Massimo Serra, Vanessa Cerisano, Rosaria Strammiello, Nicola Baldini & Piero Picci

  2. Istituto di Cancerologia, Università degli Studi di Bologna, Bologna, Italy

    Pier-Luigi Lollini & Patrizia Nanni

  3. Istituto Nazionale per la Ricerca sul Cancro-Genova, Sezione di Biotecnologie di Bologna, Bologna, Italy

    Giordano Nicoletti

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  1. Katia Scotlandi
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Correspondence to Katia Scotlandi.

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Scotlandi, K., Maini, C., Manara, M. et al. Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing's sarcoma cells. Cancer Gene Ther 9, 296–307 (2002). https://doi.org/10.1038/sj.cgt.7700442

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