Platelet activating factor inhibits the expression of matrix metalloproteinases and affects invasiveness and differentiation in a system of human neuroblastoma clones.
Platelet Activating Factor (PAF), an inflammatory bioactive lipid, has been shown to be involved in the regulation of the activity of matrix metalloproteinases (MMPs). In view of the role played by MMPs in tumor cell invasiveness, we investigated whether PAF influences MMP activity in a system of neuroblastoma clones, the AA5 and AE12 cells, isolated from the human LaN1 neuroblastoma cell line. These clones were characterized by an inverse relationship between invasiveness and differentiative capacity and by the expression of specific cell surface PAF receptors. We found that the levels of mRNAs specific for MMP-2 and for MT1-MMP, the MMP-2 activator, were reduced in both clones treated with 300 nM PAF. These changes are consistent with the reduced secretion and activation of MMP-2 found in the neuroblastoma clones exposed to PAF. These effects were accompanied by an inhibition of invasiveness through Matrigel and by a promotion of differentiation, as revealed by an increased percentage of cells with neurites. The finding that both neuroblastoma clones exposed to the metalloproteinase inhibitors, BB3103 and 1,10-phenanthroline, increased their differentiative capacity and reduced their invasiveness through Matrigel, represents a further indication that PAF modulates differentiation and invasiveness by affecting the activity of MMPs.
Barletta
Emanuela
E
Department of Experimental Pathology and Oncology, University of Florence, Italy.
Mugnai
Gabriele
G
Ruggieri
Salvatore
S
D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells / Q000201:enzymology / Q000473:pathology; D003094:Collagen; D004338:Drug Combinations; D006801:Humans; D007797:Laminin; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology*; D010972:Platelet Activating Factor / Q000494:pharmacology* / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011509:Proteoglycans; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004338:Drug Combinations; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C059485:matrigel; D003094:Collagen; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2