Research Papers:

A long pentraxin-3-derived pentapeptide for the therapy of FGF8b-driven steroid hormone-regulated cancers

Arianna Giacomini, Sara Matarazzo, Katiuscia Pagano, Laura Ragona, Sara Rezzola, Michela Corsini, Emanuela Di Salle, Marco Presta and Roberto Ronca _

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Oncotarget. 2015; 6:13790-13802. https://doi.org/10.18632/oncotarget.3831

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Arianna Giacomini1,*, Sara Matarazzo1,*, Katiuscia Pagano2, Laura Ragona2, Sara Rezzola1, Michela Corsini1, Emanuela Di Salle1, Marco Presta1 and Roberto Ronca1

1 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

2 NMR Laboratory, Istituto per lo Studio delle Macromolecole, CNR, Milan, Italy

* These authors have contributed equally to this work

Correspondence to:

Roberto Ronca, email:

Marco Presta, email:

Keywords: angiogenesis, FGF8, hormone-regulated cancer, pentraxin, peptide

Received: February 02, 2015 Accepted: March 26, 2015 Published: April 14, 2015


Fibroblast growth factor-8b (FGF8b) affects the epithelial/stromal compartments of steroid hormone-regulated tumors by exerting an autocrine activity on cancer cells and a paracrine pro-angiogenic function, thus contributing to tumor progression. The FGF8b/FGF receptor (FGFR) system may therefore represent a target for the treatment of steroid hormone-regulated tumors. The soluble pattern recognition receptor long pentraxin-3 (PTX3) binds various FGFs, including FGF2 and FGF8b, thus inhibiting the angiogenic and tumorigenic activity of androgen-regulated tumor cells. Nevertheless, the complex/proteinaceous structure of PTX3 hampers its pharmacological exploitation. In this context, the acetylated pentapeptide Ac-ARPCA-NH2 (ARPCA), corresponding to the N-terminal amino acid sequence PTX3(100-104), was identified as a minimal FGF2-binding peptide able to antagonize the biological activity of FGF2. Here, we demonstrate that ARPCA binds FGF8b and inhibits its capacity to form FGFR1-mediated ternary complexes with heparan sulphate proteoglycans. As a FGF8b antagonist, ARPCA inhibits FGFR1 activation and signalling in endothelial cells, hampering the angiogenic activity exerted in vitro and in vivo by FGF8b. Also, ARPCA suppresses the angiogenic and tumorigenic potential of prototypic androgen/FGF8b-dependent Shionogi 115 mammary carcinoma cells and of androgen/FGF8b/FGF2-dependent TRAMP-C2 prostate cancer cells. In conclusion, ARPCA represents a novel FGF8b antagonist with translational implications for the therapy of steroid hormone-regulated tumors.

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