title: Proliferation versus migration in platelet-derived growth factor signaling: the key role of endocytosis.
abstract: It is common knowledge that platelet-derived growth factor (PDGF) is a critical regulator of mesenchymal cell migration and proliferation. Nevertheless, these two cellular responses are mutually exclusive. To solve this apparent contradiction, we studied the behavior of NIH3T3 fibroblasts in response to increasing concentrations of PDGF. We found that there is strong cell proliferation induction only with PDGF concentrations >5 ng/ml, whereas the cell migration response arises starting from 1 ng/ml and is negligible at higher PDGF concentrations. According to these phenotypic evidences, our data indicate that cells display a differential activation of the main signaling pathways in response to PDGF as a function of the stimulation dose. At low PDGF concentrations, there is maximal activation of signaling pathways linked to cytoskeleton rearrangement needed for cell motility, whereas high PDGF concentrations activate pathways linked to mitogenesis induction. Our results suggest a mechanism by which cells switch from a migrating to a proliferating phenotype sensing the increasing gradient of PDGF. In addition, we propose that the cell decision to proliferate or migrate relies on different endocytotic routes of the PDGF receptor in response to different PDGF concentrations.
authors.affiliation: Dipartimento di Scienze Biochimiche, Università degli Studi di Firenze, Firenze, Italy.
authors.forename: Alina
authors.initials: A
authors.lastname: De Donatis
authors.forename: Giusy
authors.initials: G
authors.lastname: Comito
authors.forename: Francesca
authors.initials: F
authors.lastname: Buricchi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Vinci
authors.forename: Astrid
authors.initials: A
authors.lastname: Parenti
authors.forename: Anna
authors.initials: A
authors.lastname: Caselli
authors.forename: Guido
authors.initials: G
authors.lastname: Camici
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Manao
authors.forename: Giampietro
authors.initials: G
authors.lastname: Ramponi
authors.forename: Paolo
authors.initials: P
authors.lastname: Cirri
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D020830:rac1 GTP-Binding Protein