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SYK is a target of lymphocyte-derived microparticles in the induction of apoptosis of human retinoblastoma cells

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Abstract

Retinoblastoma (Rb) is an aggressive childhood cancer of the developing retina. This disease is associated with epigenetic deregulation of several cancer pathways including upregulation of the proto-oncogene spleen tyrosine kinase (SYK). We have previously demonstrated that lymphocyte-derived microparticles (LMPs) possess strong cytotoxic effect on cancer cells. This report demonstrated that LMPs have potent pro-apoptotic properties on human Rb cells, which was associated with a strong reduction of SYK expression. Perturbing SYK activity in Rb cells induced cell apoptosis and upregulated expression of p53 and p21. Interestingly, inhibition of p53 or knockdown of p21, abolished LMP-induced caspase-3 activity and cell death. Blocking oxidized phospholipid-rich LMPs with a specific antibody significantly prevented LMP-induced Rb apoptosis and reversed the expression patterns of SYK, p53, p21. In summary, our results suggest that LMPs are important pro-apoptotic regulators for Rb cells through reduction of SYK expression and upregulation of the p53–p21 pathway which ultimately activates caspase-3. These data may open unexpected avenues for the development of LMPs as a novel therapeutic strategy that would be particularly useful and relevant for the treatment of Rb.

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Acknowledgments

This research was supported by the Fonds de Recherche en Santé du Québec (FRSQ Vision Research Network) to P. Hardy. Qian Qiu is supported by the State Scholarship Fund of the Ministry of Education of Peoples’ Republic of China (20120761002).

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Authors and Affiliations

  1. Departments of Pediatrics, Hematology-Oncology and Pharmacology, University of Montréal, Montreal, QC, Canada

    Chun Yang, Houda Tahiri, Anne-Sophie Carret, Bussières Martin & Pierre Hardy

  2. Department of Pulmonology, Southwest Hospital, Third Military Medical University, Chongqing, China

    Qian Qiu, Wei Xiong & Guoxiang Liu

  3. Medical School, University of Montréal, Montreal, QC, Canada

    Mathieu Payeur

  4. Department of Ophthalmology, University of Montréal, Montreal, QC, Canada

    Rosanne Superstein, Patrick Hamel & Przemyslaw Sapieha

  5. Department of Pathology and Cell Biology, University of Montréal, Montreal, QC, Canada

    Benjamin Ellezam

  6. Charles River Laboratories Preclinicals Services, Senneville, QC, Canada

    Mark Vezina

  7. Research Center of CHU Sainte-Justine, 3175 Côte-Sainte-Catherine, Room 2714, Montreal, QC, H3T 1C5, Canada

    Pierre Hardy

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  1. Qian Qiu
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  2. Chun Yang
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Correspondence to Pierre Hardy.

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Qiu, Q., Yang, C., Xiong, W. et al. SYK is a target of lymphocyte-derived microparticles in the induction of apoptosis of human retinoblastoma cells. Apoptosis 20, 1613–1622 (2015). https://doi.org/10.1007/s10495-015-1177-2

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  • DOI: https://doi.org/10.1007/s10495-015-1177-2

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