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Biological functions of ecto-enzymes in regulating extracellular adenosine levels in neoplastic and inflammatory disease states

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Abstract

When present in the extracellular environment, the nucleoside adenosine protects cells and tissues from excessive inflammation and immune-mediated damage while promoting healing processes. This role has been highlighted experimentally using distinct disease models, including those of colitis, diabetes, asthma, sepsis, and ischemic injury. Adenosine also suppresses immune responses, as in the tumor microenvironment, assisting immune evasion while promoting angiogenesis. The mechanisms involved in adenosine signaling are addressed elsewhere in this issue. Here, the authors specifically address the generation of adenosine from extracellular nucleotides. This process is catalyzed by a series of plasma membrane ectonucleotidases, with the focus in this article on members of the CD39, CD73, and CD38 families and on their role in inflammatory and neoplastic hematological diseases. Pharmacological modulation of adenosine generation by drugs that either have or modulate ectonucleotidase function might be exploited to treat these diverse conditions.

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Acknowledgments

The work summarized in this review article was supported by: Clinician Scientist Fellowship from the Medical Research Council (UK); National Institute of Health; R01 HL094400; P01HL107152, P01 HL087203, and P01 AI045897 and Associazione Italiana Ricerca Cancro (IG #12754); Italian Ministries of Health (Bando Giovani Ricercatori 2008) and Education (Bando FIRB Giovani 2008 and Bando PRIN 2009).

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The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill, SE5 9RS, London, UK

    Maria Serena Longhi

  2. Division of Gastroenterology, and Transplant Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, 02215, USA

    Simon C. Robson

  3. James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Steven H. Bernstein

  4. Human Genetics Foundation (HuGeF) and Department of Medical Sciences, University of Turin, Turin, Italy

    Sara Serra & Silvia Deaglio

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  1. Maria Serena Longhi
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  5. Silvia Deaglio
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Correspondence to Maria Serena Longhi or Silvia Deaglio.

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Longhi, M.S., Robson, S.C., Bernstein, S.H. et al. Biological functions of ecto-enzymes in regulating extracellular adenosine levels in neoplastic and inflammatory disease states. J Mol Med 91, 165–172 (2013). https://doi.org/10.1007/s00109-012-0991-z

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