Research Papers:

Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells

Marta Nardella, Loredana Guglielmi, Carla Musa, Ilaria Iannetti, Giovanna Maresca, Donatella Amendola, Manuela Porru, Elisabetta Carico, Giuseppe Sessa, Rosalba Camerlingo, Carlo Dominici, Francesca Megiorni, Marika Milan, Claudia Bearzi, Roberto Rizzi, Giuseppe Pirozzi, Carlo Leonetti, Barbara Bucci, Delio Mercanti, Armando Felsani and Igea D’Agnano _

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Oncotarget. 2015; 6:32821-32840. https://doi.org/10.18632/oncotarget.5104

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Marta Nardella1, Loredana Guglielmi1, Carla Musa1, Ilaria Iannetti1, Giovanna Maresca1, Donatella Amendola2, Manuela Porru3, Elisabetta Carico4, Giuseppe Sessa5, Rosalba Camerlingo5, Carlo Dominici6,7, Francesca Megiorni6, Marika Milan1, Claudia Bearzi1,8, Roberto Rizzi1,8, Giuseppe Pirozzi5, Carlo Leonetti3, Barbara Bucci2, Delio Mercanti1, Armando Felsani1, Igea D'Agnano1

1Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy

2S.Pietro Hospital Fatebenefratelli, Rome, Italy

3Regina Elena Cancer Institute, Rome, Italy

4UOD Cytopathology, Department of Molecular and Clinical Medicine, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy

5Department of Experimental Oncology, National Cancer Institute–IRCCS “Fondazione G. Pascale”, Naples, Italy

6Department of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Rome, Italy

7School of Reproductive and Developmental Medicine, University of Liverpool, Liverpool, United Kingdom

8I.R.C.C.S Multimedica, Scientific and Technology Pole, Milan, Italy

Correspondence to:

Igea D'Agnano, e-mail: [email protected]

Keywords: neuroblastoma, TICs, Lamin A/C, MYCN, miRNAs

Received: April 09, 2015     Accepted: August 21, 2015     Published: September 03, 2015


Tumor-initiating cells constitute a population within a tumor mass that shares properties with normal stem cells and is considered responsible for therapy failure in many cancers. We have previously demonstrated that knockdown of the nuclear envelope component Lamin A/C in human neuroblastoma cells inhibits retinoic acid-mediated differentiation and results in a more aggressive phenotype. In addition, Lamin A/C is often lost in advanced tumors and changes in the nuclear envelope composition occur during tumor progression. Based on our previous data and considering that Lamin A/C is expressed in differentiated tissues, we hypothesize that the lack of Lamin A/C could predispose cells toward a stem-like phenotype, thus influencing the development of tumor-initiating cells in neuroblastoma. This paper demonstrates that knockdown of Lamin A/C triggers the development of a tumor-initiating cell population with self-renewing features in human neuroblastoma cells. We also demonstrates that the development of TICs is due to an increased expression of MYCN gene and that in neuroblastoma exists an inverse relationship between LMNA and MYCN expression.

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