The novel SPARC family member SMOC-2 potentiates angiogenic growth factor activity.
SMOC-2 is a novel member of the SPARC family of matricellular proteins. The purpose of this study was to determine whether SMOC-2 can modulate angiogenic growth factor activity and angiogenesis. SMOC-2 was localized in the extracellular periphery of cultured human umbilical vein endothelial cells (HUVECs). Ectopically expressed SMOC-2 was also secreted into the tissue culture medium. In microarray profiling experiments, a recombinant SMOC-2 adenovirus induced the expression of transcripts required for cell cycle progression in HUVECs. Consistent with a growth-stimulatory role for SMOC-2, its overexpression stimulated DNA synthesis in a dose-dependent manner. Overexpressed SMOC-2 also synergized with vascular endothelial growth factor or with basic fibroblast growth factor to stimulate DNA synthesis. Ectopically expressed SMOC-2 stimulated formation of network-like structures as determined by in vitro matrigel angiogenesis assays. Fetal calf serum enhanced the stimulatory effect of overexpressed SMOC-2 in this assay. Conversely, small interference RNA directed toward SMOC-2 inhibited network formation and proliferation. The angiogenic activity of SMOC-2 was also examined in experimental mice by subdermal implantation of Matrigel plugs containing SMOC-2 adenovirus. SMOC-2 adenovirus induced a 3-fold increase in the number of cells invading Matrigel plugs when compared with a control adenoviral vector. Basic fibroblast growth factor and SMOC-2 elicited a synergistic effect on cell invasion. Taken together, our results demonstrate that SMOC-2 is a novel angiogenic factor that potentiates angiogenic effects of growth factors.
Rocnik
Edward F
EF
Molecular Cardiology, Whitaker Cardiovascular Institute and Department of Genetics and Genomics, Boston University School of Medicine, Boston, Massachusetts 02118, USA. efrocnik@yahoo.com
Liu
Peijun
P
Sato
Kaori
K
Walsh
Kenneth
K
Vaziri
Cyrus
C
D000256:Adenoviridae / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007797:Laminin / Q000737:chemistry; D051379:Mice; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000737:chemistry; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000737:chemistry
D020533:Angiogenesis Inhibitors; D002135:Calcium-Binding Proteins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C513851:SMOC-2 protein, mouse; C476827:SMOC2 protein, human; C059485:matrigel; D003094:Collagen