title: Long pentraxin-3 inhibits epithelial-mesenchymal transition in melanoma cells.
abstract: During melanoma progression, malignant melanocytes are reprogrammed into mesenchymal-like cells through to an epithelial-mesenchymal transition (EMT) process associated with the acquisition of an invasive, prometastatic phenotype. The fibroblast growth factor-2 (FGF2)/FGF receptor (FGFR) system plays a pivotal role in melanoma, leading to autocrine/paracrine induction of tumor cell proliferation and angiogenesis. Long pentraxin-3 (PTX3) interacts with FGF2, and other FGF family members, inhibiting FGF-dependent neovascularization and tumor growth. Here, PTX3 protein and the PTX3-derived acetylated pentapeptide Ac-ARPCA-NH2 inhibit FGF2-driven proliferation and downstream FGFR signaling in murine melanoma B16-F10 cells. Moreover, human PTX3-overexpressing hPTX_B16-F10 cells are characterized by the reversed transition from a mesenchymal to an epithelial-like appearance, inhibition of cell proliferation, loss of clonogenic potential, reduced motility and invasive capacity, downregulation of various mesenchymal markers, and upregulation of the epithelial marker E-cadherin. Accordingly, PTX3 affects cell proliferation and EMT transition in human A375 and A2058 melanoma cells. Also, hPTX_B16-F10 cells showed a reduced tumorigenic and metastatic activity in syngeneic C57BL/6 mice. In conclusion, PTX3 inhibits FGF/FGFR-driven EMT in melanoma cells, hampering their tumorigenic and metastatic potential. These data represent the first experimental evidence about a nonredundant role of the FGF/FGFR system in the modulation of the EMT process in melanoma and indicate that PTX3 or its derivatives may represent the basis for the design of novel therapeutic approaches in FGF/FGFR-dependent tumors, including melanoma.
authors.affiliation: Corresponding Author: Marco Presta, Department of Molecular and Translational Medicine, School of Medicine, Viale Europa 11, 25123 Brescia, Italy. presta@med.unibs.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ronca
authors.forename: Emanuela
authors.initials: E
authors.lastname: Di Salle
authors.forename: Arianna
authors.initials: A
authors.lastname: Giacomini
authors.forename: Daria
authors.initials: D
authors.lastname: Leali
authors.forename: Patrizia
authors.initials: P
authors.lastname: Alessi
authors.forename: Daniela
authors.initials: D
authors.lastname: Coltrini
authors.forename: Cosetta
authors.initials: C
authors.lastname: Ravelli
authors.forename: Sara
authors.initials: S
authors.lastname: Matarazzo
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Marco
authors.initials: M
authors.lastname: Presta
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D002642:Chick Embryo; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008546:Melanoma, Experimental; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000494:pharmacology*; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D016222:Fibroblast Growth Factor 2; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins