Angiogenesis is an indispensable prerequisite for the progression and metastasis of solid malignancies. Tumor angiogenesis appears to be governed by alterations of tumor suppressor or oncogenes operant in a broad range of tumors. We have addressed this issue in neuroblastoma, a malignancy characterized by the near-exclusive amplification and overexpression of the N-Myc oncogene. Here, we report that N-Myc overexpression results in down-regulation of interleukin-6 (IL-6) and that IL-6 is an inhibitor of endothelial cell proliferation and VEGF-induced rabbit corneal angiogenesis. STAT3 is instrumental for IL-6 activity as infection with adenoviruses expressing a phosphorylation deficient STAT3 mutant renders endothelial cells insensitive to the antiproliferative action of IL-6. Finally, though IL-6 does not influence neuroblastoma cell growth, IL-6-expressing xenograft tumors in mice exhibit reduced neovascularization and suppressed growth. Our data shed new light on the mechanisms by which N-myc oncogene amplification enhances the malignant phenotype in neuroblastomas.

E., H., C., M., A., Z., H., R., Morbidelli, L., H., A., et al. (2002). N-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and supresses neuroblastoma tumor growth. ONCOGENE, 21(22), 3552-3561.

N-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and supresses neuroblastoma tumor growth

MORBIDELLI, LUCIA;ZICHE, MARINA;
2002

Abstract

Angiogenesis is an indispensable prerequisite for the progression and metastasis of solid malignancies. Tumor angiogenesis appears to be governed by alterations of tumor suppressor or oncogenes operant in a broad range of tumors. We have addressed this issue in neuroblastoma, a malignancy characterized by the near-exclusive amplification and overexpression of the N-Myc oncogene. Here, we report that N-Myc overexpression results in down-regulation of interleukin-6 (IL-6) and that IL-6 is an inhibitor of endothelial cell proliferation and VEGF-induced rabbit corneal angiogenesis. STAT3 is instrumental for IL-6 activity as infection with adenoviruses expressing a phosphorylation deficient STAT3 mutant renders endothelial cells insensitive to the antiproliferative action of IL-6. Finally, though IL-6 does not influence neuroblastoma cell growth, IL-6-expressing xenograft tumors in mice exhibit reduced neovascularization and suppressed growth. Our data shed new light on the mechanisms by which N-myc oncogene amplification enhances the malignant phenotype in neuroblastomas.
E., H., C., M., A., Z., H., R., Morbidelli, L., H., A., et al. (2002). N-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and supresses neuroblastoma tumor growth. ONCOGENE, 21(22), 3552-3561.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/29226
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