1. Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy
- Author
-
Ronca, Roberto, Giacomini, Arianna, Di Salle, Emanuela, Coltrini, Daniela, Pagano, Katiuscia, Ragona, Laura, Matarazzo, Sara, Rezzola, Sara, Maiolo, Daniele, Torrella, Rubben, Moroni, Elisabetta, Mazzieri, Roberta, Escobar, Giulia, Mor, Marco, Colombo, Giorgio, and Presta, Marco
- Subjects
Male ,pentraxin, FGF, FGFR, cancer, cancer therapy, angiogenesis ,Cancer Research ,FGF2 ,Angiogenesis ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Fibroblast growth factor ,Metastasis ,angiogenesis ,chemistry.chemical_compound ,Neoplasms ,FGF ,structural biology ,Cells, Cultured ,Molecular Structure ,Neovascularization, Pathologic ,biology ,FGFR ,Reverse Transcriptase Polymerase Chain Reaction ,Chemistry ,Cell Cycle ,PTX3 ,Small molecule ,Angiopoietin receptor ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,Serum Amyloid P-Component ,C-Reactive Protein ,Oncology ,Fibroblast growth factor receptor ,cancer therapy ,Female ,Cell Survival ,pentraxin ,Blotting, Western ,Cancer therapy ,Mice, Nude ,Mice, Transgenic ,Small Molecule Libraries ,Trap (computing) ,antineoplastic molecule ,Cell Line, Tumor ,medicine ,cancer ,Animals ,Humans ,Pentraxin-3 ,Growth factor ,Cancer ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,Molecular biology ,NMR ,Fibroblast Growth Factors ,Mice, Inbred C57BL ,Cancer cell ,biology.protein ,Cancer research ,Derivative (chemistry) - 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.
- Published
- 2015