1. Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy.
- Author
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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, and Presta M
- Subjects
- Animals, Blotting, Western, C-Reactive Protein metabolism, Cell Cycle drug effects, Cell Cycle genetics, Cell Line, Tumor, Cell Survival drug effects, Cell Survival genetics, Cells, Cultured, Female, Fibroblast Growth Factors metabolism, Fibroblast Growth Factors pharmacology, Humans, Kaplan-Meier Estimate, Male, Mice, Inbred C57BL, Mice, Nude, Mice, Transgenic, Molecular Structure, Neoplasms metabolism, Neoplasms therapy, Neovascularization, Pathologic genetics, Neovascularization, Pathologic metabolism, Reverse Transcriptase Polymerase Chain Reaction, Serum Amyloid P-Component metabolism, Small Molecule Libraries chemistry, Small Molecule Libraries pharmacology, Tumor Burden drug effects, Tumor Burden genetics, Xenograft Model Antitumor Assays methods, C-Reactive Protein genetics, Fibroblast Growth Factors genetics, Gene Expression Regulation, Neoplastic, Neoplasms genetics, Serum Amyloid P-Component genetics
- 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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