In the absence of IGF-1 signaling, IFN-γ suppresses human malignant T-cell growth

Laura Conti, Gabriella Regis, Angela Longo, Paola Bernabei, Roberto Chiarle, Mirella Giovarelli, Francesco Novelli

Research output: Contribution to journalArticle

Abstract

Several approaches to target insulin-like growth factor-1 (IGF-1) signaling have resulted in the inhibition of the growth of a broad range of tumor cells. Malignant T cells are insensitive to the antiproliferative effects of the interferon-γ (IFN-γ)/signal transducer and activator of transcription 1 (STAT1) pathway because of the IGF-1-dependent internalization of the IFN-γR2 signaling chain. Here we show that human malignant T cells are also resistant to the growth inhibitory effect of both the IGF-1 receptor-specific inhibitor picropodophyllin (PPP) and retrovirus-mediated gene transfer of a dominant negative IGF-1 receptor. However, blockade of IGF-1 receptor perturbs IFN-γR2 internalization and induces its cell surface accumulation in malignant T cells. This allows the reinstatement of the IFN-γ-induced STAT1 activation, a high expression of proapoptotic molecules, and the suppression of malignant T-cell growth both in vitro and in vivo in a severe combined immunodeficiency (SCID) mouse model. These data indicate that the inhibition of IGF-1 signaling combined with IFN-γ administration could be a promising approach to suppress the growth of neoplastic T cells resistant to each treatment on its own.

Original languageEnglish
Pages (from-to)2496-2504
Number of pages9
JournalBlood
Volume109
Issue number6
DOIs
Publication statusPublished - Mar 15 2007

    Fingerprint

ASJC Scopus subject areas

  • Hematology

Cite this

Conti, L., Regis, G., Longo, A., Bernabei, P., Chiarle, R., Giovarelli, M., & Novelli, F. (2007). In the absence of IGF-1 signaling, IFN-γ suppresses human malignant T-cell growth. Blood, 109(6), 2496-2504. https://doi.org/10.1182/blood-2006-07-034231