Recombinant platelet factor 4: a therapeutic, anti-neoplastic chimera?

Seminars in Thrombosis and Hemostasis
Giuseppe Lippi, Emmanuel J Favaloro

Abstract

Angiogenesis plays a pivotal role in many serious and life-threatening disorders (e.g., cancer, atherosclerosis, diabetes, arthritis, psoriasis, nephropathy, and retinopathy) and is regulated by a delicate equilibrium between a variety of pro- and anti-angiogenic factors. Although recombinant platelet factor 4 (PF4) was originally developed and evaluated as a clinical alternative to protamine for heparin neutralization, the current scientific evidence supports a role for this protein and derivative peptides in inhibiting tumor growth and spread, by suppression of tumor-induced neovascularization in many different types of solid tumors. As a heparin-binding tetramer, recombinant PF4 interferes with several steps of endothelial cell proliferation, migration, and angiogenesis, regulates apoptotic death through activation of distinct signal transduction pathways, inhibits growth factor receptor binding, amplifies the inflammatory response of natural killer cells through regulation of cytokines production, and induces and maintains a nonspecific immune response to cancer cells. These biological evidences paved the way for the development and marketing of novel PF4-based angiostatic agents characterized by reduced toxicity and improv...Continue Reading

Citations

Feb 26, 2013·European Journal of Internal Medicine·Hadi A GoubranMagdy El-Ekiaby
Jul 16, 2014·Seminars in Oncology·Hadi A GoubranThierry Burnouf
Dec 27, 2013·Mediators of Inflammation·Jeffry CutreraShulin Li
Dec 17, 2014·Cytokine & Growth Factor Reviews·Katrien Van RaemdonckSofie Struyf
May 26, 2017·Pediatric Blood & Cancer·Ricardo J FloresTsz-Kwong Man
Apr 14, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paola ChiodelliMarco Rusnati
Oct 11, 2012·Bioscience, Biotechnology, and Biochemistry·Yitao DuanHe Huang
Jan 10, 2018·Genome Biology·Timothy E Van BaakRobert A Waterland

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