Inhibition of neuroblastoma cell growth by TREX1-mutated human lymphocytes

  • Authors:
    • A. Pulliero
    • B. Marengo
    • C. Domenicotti
    • M. G. Longobardi
    • E. Fazzi
    • S. Orcesi
    • M. Bianchi
    • U. Balottin
    • A. Izzotti
  • View Affiliations

  • Published online on: February 22, 2012     https://doi.org/10.3892/or.2012.1696
  • Pages: 1689-1694
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Abstract

T lymphocytes play a major role in counteracting cancer occurrence and development. Immune therapies against cancer are focused on eliciting a cytotoxic T cell response. This anticancer activity is related to a variety of mechanisms including the activation of cytokines and proapoptotic mediators. Interferon α is an established inhibitor of cancer cell growth. A clinical situation involving the coexistence of high interferon α levels and lymphocyte activation is the Aicardi-Goutières syndrome, a progressive encephalopathy arising usually during the first year of life characterized by intracranial basal ganglia calcifications, leukodystrophy and microcephaly. Aicardi-Goutières syndrome 1 mutation silences the TREX1 gene, a major endogenous nuclease. The in vitro study presented herein evaluates the efficacy of the TREX1 mutation in potentiating the anticancer properties of T cells. A TREX1-mutated lymphocyte cell line was derived from an Aicardi-Goutières syndrome patient and co-cultured with neuroblastoma cells and vascular endothelial cells in the presence of interferon α. TREX1-mutated lymphocytes exerted marked inhibitory action on neuroblastoma cell growth. Cathepsin D was recognized by qPCR as the main mediator produced by TREX1-mutated lymphocytes involved in the inhibition of neuroblastoma cell growth. These effects were enhanced in the presence of interferon α. Similar inhibitory effects in cell growth were exerted by TREX1-mutated lymphocytes towards vascular endothelial cell angiogenesis as evaluated on Matrigel. The results obtained provide evidence that mutations of the TREX1 gene increase the capability of T-lymphocytes to inhibit growth of neoplastic neuronal cells and related angiogenesis.

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May 2012
Volume 27 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Pulliero A, Marengo B, Domenicotti C, Longobardi MG, Fazzi E, Orcesi S, Bianchi M, Balottin U and Izzotti A: Inhibition of neuroblastoma cell growth by TREX1-mutated human lymphocytes. Oncol Rep 27: 1689-1694, 2012
APA
Pulliero, A., Marengo, B., Domenicotti, C., Longobardi, M.G., Fazzi, E., Orcesi, S. ... Izzotti, A. (2012). Inhibition of neuroblastoma cell growth by TREX1-mutated human lymphocytes. Oncology Reports, 27, 1689-1694. https://doi.org/10.3892/or.2012.1696
MLA
Pulliero, A., Marengo, B., Domenicotti, C., Longobardi, M. G., Fazzi, E., Orcesi, S., Bianchi, M., Balottin, U., Izzotti, A."Inhibition of neuroblastoma cell growth by TREX1-mutated human lymphocytes". Oncology Reports 27.5 (2012): 1689-1694.
Chicago
Pulliero, A., Marengo, B., Domenicotti, C., Longobardi, M. G., Fazzi, E., Orcesi, S., Bianchi, M., Balottin, U., Izzotti, A."Inhibition of neuroblastoma cell growth by TREX1-mutated human lymphocytes". Oncology Reports 27, no. 5 (2012): 1689-1694. https://doi.org/10.3892/or.2012.1696