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Gc protein-derived macrophage-activating factor (GcMAF) stimulates cAMP formation in human mononuclear cells and inhibits angiogenesis in chick embryo chorionallantoic membrane assay

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Abstract

The effects of Gc protein-derived macrophage-activating factor (GcMAF) have been studied in cancer and other conditions where angiogenesis is deregulated. In this study, we demonstrate for the first time that the mitogenic response of human peripheral blood mononuclear cells (PBMCs) to GcMAF was associated with 3′-5′-cyclic adenosine monophosphate (cAMP) formation. The effect was dose dependent, and maximal stimulation was achieved using 0.1 ng/ml. Heparin inhibited the stimulatory effect of GcMAF on PBMCs. In addition, we demonstrate that GcMAF (1 ng/ml) inhibited prostaglandin E1- and human breast cancer cell-stimulated angiogenesis in chick embryo chorionallantoic membrane (CAM) assay. Finally, we tested different GcMAF preparations on CAM, and the assay proved to be a reliable, reproducible and inexpensive method to determine the relative potencies of different preparations and their stability; we observed that storage at room temperature for 15 days decreased GcMAF potency by about 50%. These data could prove useful for upcoming clinical trials on GcMAF.

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Acknowledgments

This research project has been subsidized by the University of Firenze (Progetti di Ricerca di Ateneo, ex 60%) and by the Italian Ministry of Health (Progetto Strategico “La Medicina di genere come obiettivo strategico per la sanità pubblica: l’appropriatezza della cura per la tutela della salute della donna”). We are indebted with Prof. N. Yamamoto for providing GcMAF and inspiring discussion.

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Authors and Affiliations

  1. Department of Anatomy, Histology and Forensic Medicine, University of Firenze, Florence, Italy

    Stefania Pacini, Gabriele Morucci, Tiziana Punzi & Massimo Gulisano

  2. Department of Experimental Pathology and Oncology, University of Firenze, Viale Morgagni 50, 50134, Florence, Italy

    Marco Ruggiero

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  1. Stefania Pacini
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  2. Gabriele Morucci
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  3. Tiziana Punzi
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  4. Massimo Gulisano
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  5. Marco Ruggiero
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Correspondence to Marco Ruggiero.

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Pacini, S., Morucci, G., Punzi, T. et al. Gc protein-derived macrophage-activating factor (GcMAF) stimulates cAMP formation in human mononuclear cells and inhibits angiogenesis in chick embryo chorionallantoic membrane assay. Cancer Immunol Immunother 60, 479–485 (2011). https://doi.org/10.1007/s00262-010-0953-7

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