2. Academic Validation
  3. Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy

Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy

  • Cancer Cell. 2015 Aug 10;28(2):225-39. doi: 10.1016/j.ccell.2015.07.002.
Roberto Ronca 1,  Arianna Giacomini 2,  Emanuela Di Salle 2,  Daniela Coltrini 2,  Katiuscia Pagano 3,  Laura Ragona 3,  Sara Matarazzo 2,  Sara Rezzola 2,  Daniele Maiolo 4,  Rubben Torrella 5,  Elisabetta Moroni 5,  Roberta Mazzieri 6,  Giulia Escobar 7,  Marco Mor 8,  Giorgio Colombo 5,  Marco Presta 9
Affiliations

Affiliations

  • 1 Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. Electronic address: roberto.ronca@unibs.it.
  • 2 Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
  • 3 NMR Laboratory, Istituto per lo Studio delle Macromolecole, CNR, 20133 Milan, Italy.
  • 4 Chemistry for Technologies Laboratory and INSTM, School of Engineering, University of Brescia, 25123 Brescia, Italy.
  • 5 Istituto di Chimica del Riconoscimento Molecolare, CNR, 20133 Milan, Italy.
  • 6 University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD 4102, Australia.
  • 7 San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy; Vita Salute San Raffaele University, 20132 Milan, Italy.
  • 8 Department of Pharmacy, University of Parma, 43121 Parma, Italy.
  • 9 Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. Electronic address: marco.presta@unibs.it.
PMID: 26267536 DOI: 10.1016/j.ccell.2015.07.002
Abstract

The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) system plays a crucial role in Cancer by affecting tumor growth, angiogenesis, drug resistance, and escape from anti-angiogenic anti-vascular endothelial growth factor therapy. The soluble pattern recognition receptor long-pentraxin 3 (PTX3) acts as a multi-FGF antagonist. Here we demonstrate that human PTX3 overexpression in transgenic mice driven by the Tie2 promoter inhibits tumor growth, angiogenesis, and metastasis in heterotopic, orthotopic, and autochthonous FGF-dependent tumor models. Using pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2, we identified a small-molecule chemical (NSC12) that acts as an extracellular FGF trap with significant implications in Cancer therapy.

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    99.07%, Anticancer Agent