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Extracellular matrix molecules regulate endothelial cell migration stimulated by lysophosphatidic acid. J Thromb Haemost 2004 Sep;2(9):1645-56



Pubmed ID




Scopus ID

2-s2.0-13244273416 (requires institutional sign-in at Scopus site)   37 Citations


BACKGROUND: Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are lipids that bind G-protein coupled receptors and differentially promote transmigration of endothelial cells.

OBJECTIVE: To determine if endothelial cell transmigration stimulated by LPA, not S1P, is dependent on the extracellular matrix.

METHODS: Bovine pulmonary artery (BPAE) endothelial cell transmigration and locomotion were measured using a modified-Boyden chamber and video microscopy, respectively. Results were related to strength of adhesion and characteristics of cell adhesive contacts.

RESULTS AND CONCLUSIONS: BPAEs responded to LPA by transmigration through gelatin- or collagen-coated filters, but not through fibronectin-, vitronectin-, or fibrinogen-coated filters. Fewer cells adhered to collagen or gelatin than to fibronectin in a static cell adhesion assay or after application of a g-force to detach cells. Video microscopy revealed that S1P stimulates large lamellipodia on two-dimensional fibronectin substrate. LPA stimulated lamellipodia on fibronectin, but the trailing edge remained attached, resulting in sting ray-shaped cells in video microscopy. LPA-treated cells on gelatin released the trailing edge. To understand how the extracellular matrix may regulate endothelial cell shape during movement, we surveyed changes in focal adhesion proteins. More Hic-5, a paxillin homolog, was detected in the detergent insoluble fraction of BPAEs attached to gelatin than fibronectin. No such difference was found in paxillin. In BPAEs, Hic-5 was localized to smaller punctate structures on fibronectin and longer, thinner focal adhesions on gelatin. These results indicated that localization of Hic-5 and strength of adhesion correlate with endothelial cell transmigration stimulated by LPA, but not with transmigration stimulated by S1P.

Author List

Panetti TS, Hannah DF, Avraamides C, Gaughan JP, Marcinkiewicz C, Huttenlocher A, Mosher DF


Dawn Felicity Wolfgram MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Adhesion
Cell Movement
Cells, Cultured
Cytoskeletal Proteins
DNA-Binding Proteins
Endothelium, Vascular
Extracellular Matrix Proteins
Intracellular Signaling Peptides and Proteins
LIM Domain Proteins
Microscopy, Video