tautomycetin and Carcinoma--Lewis-Lung

Motility of endothelial cells is a requirement for the vascularization of solid malignancies. While tumors have been shown to produce a host of angiogenic factors, including TGF-β, the mechanisms by which such factors regulate endothelial cell motility have not yet been defined. Thus, the role of the serine/threonine phosphatase PP-1 in regulating endothelial cell motility and cytoskeletal architecture was studied. The present study demonstrated that TGF-β stimulation of motility is dependent on PP-1. Likewise, TGF-β was shown to up-regulate paxillin expression through a process that was PP-1 dependent. The interplay between PP-1 and TGF-β was further observed by the induction of cell rounding and the loss of paxillin-actin co precipitations upon PP-1 inhibition and the compensation for these effects by TGF-β. Studies initiated to determine how PP-1 might regulate motility showed its role in maintaining cytoskeletal organization and its capacity to directly dephosphorylate the focal adhesion scaffolding protein paxillin. These studies suggest that the interplay between TGF-β and PP-1 regulates the motility of endothelial cells that is critical to the process of angiogenesis.

Topics: Actins; Animals; Carcinoma, Lewis Lung; Cell Movement; Culture Media, Conditioned; Cytoskeleton; Endothelial Cells; Focal Adhesions; Furans; Humans; Lipids; Mice; Paxillin; Phosphorylation; Protein Phosphatase 1; Transforming Growth Factor beta; Up-Regulation