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

Roberto Ronca, Arianna Giacomini, Emanuela Di Salle, Daniela Coltrini, Katiuscia Pagano, Laura Ragona, Sara Matarazzo, Sara Rezzola, Daniele Maiolo, Rubben Torrella, Elisabetta Moroni, Roberta Mazzieri, Giulia Escobar, Marco Mor, Giorgio Colombo, Marco Presta

Research output: Contribution to journalArticle

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. Ronca et al. show that overexpression of long-pentraxin 3 (PTX3) in mice inhibits the growth of FGF-dependent tumor models. On the basis of pharmacophore modeling of PTX3-FGF2 interaction, they identify a small molecule that acts as an extracellular FGF trap and inhibits FGF-dependent tumor growth in mice.

Original languageEnglish
Pages (from-to)225-239
Number of pages15
JournalCancer Cell
Volume28
Issue number2
DOIs
Publication statusPublished - Aug 10 2015

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ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology
  • Medicine(all)

Cite this

Ronca, R., Giacomini, A., Di Salle, E., Coltrini, D., Pagano, K., Ragona, L., Matarazzo, S., Rezzola, S., Maiolo, D., Torrella, R., Moroni, E., Mazzieri, R., Escobar, G., Mor, M., Colombo, G., & Presta, M. (2015). Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy. Cancer Cell, 28(2), 225-239. https://doi.org/10.1016/j.ccell.2015.07.002