The Novel Sparc Family Member Smoc-2 Potentiates Angiogenic Growth Factor Activity.
From: Molecular Cardiology, Whitaker Cardiovascular Institute and Department of Genetics and Genomics, Boston University School of Medicine, Boston, Massachusetts 02118, USA. efrocnik@yahoo.com
The Journal of biological chemistry
- Publish Date: Aug 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 32
- Pages: 22855-64
- Medium: Print
- Language: English
- Citation (JAMA): Rocnik Edward F, Liu Peijun, Sato Kaori, et al. The Novel Sparc Family Member Smoc-2 Potentiates Angiogenic Growth Factor Activity.. J. Biol. Chem. Aug 2006;281:22855-64
Abstract
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.
Mesh Headings (Keywords): Adenoviridae, Angiogenesis Inhibitors, Animals, Calcium-Binding Proteins, Cell Cycle, Cells, Cultured, Collagen, Drug Combinations, Endothelium, Vascular, Humans, Laminin, Mice, Neovascularization, Physiologic, Proteoglycans, RNA, Small Interfering, Recombinant Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16774925
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