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J Biol Chem, Vol. 275, Issue 18, 13924-13932, May 5, 2000

Retrovirally Mediated Expression of Decorin by Macrovascular Endothelial Cells
EFFECTS ON CELLULAR MIGRATION AND FIBRONECTIN FIBRILLOGENESIS IN VITRO^*

Michael G. Kinsella^§, Jens W. Fischer, David P. Mason^¶, and Thomas N. Wight

From the Departments of Pathology and ^¶ Surgery, University of Washington, Seattle, Washington 98195

Decorin is a member of the widely expressed family of small leucine-rich proteoglycans. In addition to a primary role as a modulator of extracellular matrix protein fibrillogenesis, decorin can inhibit the cellular response to growth factors. Decorin expression is induced in endothelial cells during angiogenesis, but not when migration and proliferation are stimulated. Thus, decorin may support the formation of the fibrillar pericellular matrix that stabilizes the differentiated endothelial phenotype during the later stages of angiogenesis. Therefore, we tested whether constitutive decorin expression alone could modify endothelial cell migration and proliferation or affect pericellular matrix formation. To this end, replication-defective retroviral vectors were used to stably express bovine decorin, which was detected by Northern and Western blotting. The migration of endothelial cells that express decorin is significantly inhibited in both monolayer outgrowth and microchemotaxis chamber assays. The inhibition of cell migration by decorin was not accompanied by decreased proliferation. In addition, endothelial cells that express decorin assemble an extensive fibrillar fibronectin matrix more rapidly than control cells as assessed by immunocytochemical and fibronectin fibrillogenesis assays. These observations suggest that cell migration may be modulated by the influence of decorin on the assembly of the cell-associated extracellular matrix.

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