1. ¹ENEA Research Center Casaccia, Biotechnology Unit, Section of Toxicology and Biomedical Sciences, Via Angullarese, 301, 00060 S. Maria di Galeria, Rome, Italy
2. ²Kimmel Cancer Center, Thomas Jefferson University, 19107 Philadelphia, PA, USA

Correspondence: G Raschellà, ENEA Research Center Casaccia, Biotechnology Unit, Section of Toxicology and Biomedical Sciences, Via Anguillarese, 301, 00060 S. Maria di Galeria, Rome, Italy. Tel: +39-063048-3172; Fax: +39-063048-6559; E-mail: raschella@casaccia.enea.it

Received 27 May 2004; Revised 28 October 2004; Accepted 2 November 2004; Published online 24 December 2004.

Abstract

Signal transduction through the IGF axis is implicated in proliferation, differentiation and survival during development and adult life. The IGF axis includes the IGF binding proteins (IGFBPs) that bind IGFs with high affinity and modulate their activity. In neuroblastoma (NB), a malignant childhood tumor, we found that IGFBP-5 is frequently expressed. Since NB is an IGF2-sensitive tumor, we investigated the relevance and the function of endogenous IGFBP-5 in LAN-5 and in SY5Y(N) cell lines transfected with micro and small interfering RNAs directed to IGFBP-5 mRNA. Cells in which IGFBP-5 expression was suppressed were growth-inhibited and more prone to apoptosis than the parental cell line and controls. Apoptosis was further enhanced by X-ray irradiation. The ability of these cells to undergo neuronal differentiation was impaired after IGFBP-5 inhibition but the effect was reversed by exposure to recombinant IGFBP-5. Together, these data demonstrate the importance of IGFBP-5 for NB cell functions and suggest that IGFBP-5 might serve as a novel therapeutic target in NB.