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Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing's sarcoma cells.
Cancer Gene Ther. 2002 Mar; 9(3):296-307.CG

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.

Authors+Show Affiliations

Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy. katia.scotlandi@ior.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11896447

Citation

Scotlandi, Katia, et al. "Effectiveness of Insulin-like Growth Factor I Receptor Antisense Strategy Against Ewing's Sarcoma Cells." Cancer Gene Therapy, vol. 9, no. 3, 2002, pp. 296-307.
Scotlandi K, Maini C, Manara MC, et al. Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing's sarcoma cells. Cancer Gene Ther. 2002;9(3):296-307.
Scotlandi, K., Maini, C., Manara, M. C., Benini, S., Serra, M., Cerisano, V., Strammiello, R., Baldini, N., Lollini, P. L., Nanni, P., Nicoletti, G., & Picci, P. (2002). Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing's sarcoma cells. Cancer Gene Therapy, 9(3), 296-307.
Scotlandi K, et al. Effectiveness of Insulin-like Growth Factor I Receptor Antisense Strategy Against Ewing's Sarcoma Cells. Cancer Gene Ther. 2002;9(3):296-307. PubMed PMID: 11896447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing's sarcoma cells. AU - Scotlandi,Katia, AU - Maini,Cecilia, AU - Manara,Maria Cristina, AU - Benini,Stefania, AU - Serra,Massimo, AU - Cerisano,Vanessa, AU - Strammiello,Rosaria, AU - Baldini,Nicola, AU - Lollini,Pier-Luigi, AU - Nanni,Patrizia, AU - Nicoletti,Giordano, AU - Picci,Piero, PY - 2001/12/13/received PY - 2002/3/16/pubmed PY - 2002/5/30/medline PY - 2002/3/16/entrez SP - 296 EP - 307 JF - Cancer gene therapy JO - Cancer Gene Ther VL - 9 IS - 3 N2 - 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. SN - 0929-1903 UR - https://www.unboundmedicine.com/medline/citation/11896447/Effectiveness_of_insulin_like_growth_factor_I_receptor_antisense_strategy_against_Ewing's_sarcoma_cells_ L2 - https://doi.org/10.1038/sj.cgt.7700442 DB - PRIME DP - Unbound Medicine ER -