Peroxisome proliferator-activated receptor-γ ligands alter breast cancer cell motility through modulation of the plasminogen activator system

We investigated peroxisome proliferator-activated receptor-γ (ppar-γ) ligands effect on cell motility and the plasminogen activator system using normal mcf-10a and malignant mcf-10ca1 cell lines. ciglitazone reduced both wound-induced migration and chemotaxis. however,the effect was not reversed with pretreatment of cells with the ppar-γ-specific antagonist gw9662. immunoblot analysis of conditioned media showed ciglitazone decreased plasminogen activator inhibitor-1 (pai-1) in both cell lines; this effect was also unaltered by ppar-γ antagonism. alternatively,treatment with the ω-6 fatty acid arachidonic acid (ara),but not the ω-3 fatty acid docosahexanoic acid,increased both mcf-10a cell migration and cell surface upa activity. pretreatment with a ppar-γ antagonist reversed these effects,suggesting that ara mediates its effect on cell motility and upa activity through ppar-γ activation. collectively,the data suggest ppar-γ ligands have a differential effect on normal and malignant cell migration and the plasminogen activation system,resulting from ppar-γ-dependent and ppar-γ-independent effects. copyright © 2011 jennifer c. carter and frank c. church.