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PNAEμ can significantly reduce Burkitt's lymphoma tumor burden in a SCID mice model: cells dissemination similar to the human disease

Cancer Gene Therapy volume 16, pages 786–793 (2009)Cite this article

Abstract

In human Burkitt's Lymphoma (BL) BRG cells, a t(8;14) translocation, placing c-myc near the Eμ enhancer of the H chain locus, causes tumor expansion. Earlier, we showed that a peptide nucleic acid complementary to the Eμ sequence (PNAEμ), specifically inhibited the expression of translocated c-myc and impaired the growth of BRG cells-induced subcutaneous tumors in mice suffering from severe combined immunodeficiency (SCID). In this study, the therapeutic potential of PNAEμ was evaluated in a systemic mouse model. BRG-BL cells transfected with the luciferase gene were inoculated intravenously into SCID mice resulting in a preferential expansion, similar to the one of human adult patients, in the abdominal cavity, central nervous system and bone marrow. The mice were chronically injected intraperitoneally either with PNAEμ or with control PNA. The treatment was stopped when the control animals developed severe neurological symptoms. As detected both by inspection at necropsy and imaging, overall tumor growth in PNAEμ-treated mice decreased by >80%. Histological and immunohistochemical studies showed, only in PNAEμ-treated mice, a substantially reduced BL cell growth at the major sites of invasion and vast areas of necrosis in the lymphomatous tissues, with concomitant c-myc expression downregulation. Altogether, the data support the therapeutic potential of PNAEμ in human adult BL.

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Acknowledgements

This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (MF); FIRB RBIP06LCA9 (MF); ‘Rare Diseases’ Italy- USA 2006, N 526D/18 (GC); Associazione Italiana Leucemie (AIL), and Sez. Francesca Lanzone, SP (SR), Compagnia San Paolo (MC); SM was supported by a fellowship from the Fondazione Italiana per la Ricerca sul Cancro (FIRC).

We thank Ms Patrizia Mosca for technical assistance in performing the immunohistochemistry and Mr Alessandro Paganelli for the histological analysis. We are indebted to Dr Jennifer McMermott for the critical revision of the manuscript and to Dr Claudia Bolognesi for the statistical analysis.

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Author notes

  1. S Matis and M R Mariani: These two authors contributed equally to this work.

Authors and Affiliations

  1. S.C. Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy

    S Matis, M R Mariani, G Cutrona, L C Boffa & M Ferrarini

  2. S.S. Sperimentazione su Modelli Animali, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy

    M Cilli & F Piccardi

  3. S.C. Oncologia Sperimentale F, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy

    A Daga

  4. DIMES, Biochemistry Section, and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy

    G Damonte, E Millo & F Fedeli

  5. UO Anatomia ed Istologia Patologica, La Spezia, Italy

    M Moroni & S Roncella

  6. DOBIG, Biochemistry Section, and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy

    M Ferrarini

Authors
  1. S Matis
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  2. M R Mariani
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  3. G Cutrona
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  4. M Cilli
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  7. G Damonte
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  8. E Millo
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  9. M Moroni
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  11. F Fedeli
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  12. L C Boffa
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Corresponding author

Correspondence to L C Boffa.

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Matis, S., Mariani, M., Cutrona, G. et al. PNAEμ can significantly reduce Burkitt's lymphoma tumor burden in a SCID mice model: cells dissemination similar to the human disease. Cancer Gene Ther 16, 786–793 (2009). https://doi.org/10.1038/cgt.2009.26

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  • DOI: https://doi.org/10.1038/cgt.2009.26

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