The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

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 dosedependent 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.

Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis

“…25 Only the function of SMOC2 reported previously involves stimulation of endothelial cell proliferation. 26 In comparison with normal cartilage, SMOC-2 mRNA expression was higher in osteoarthritis cartilage.…”

Late SV40 Factor (LSF) Enhances Angiogenesis by Transcriptionally Up-regulating Matrix Metalloproteinase-9 (MMP-9)

“…Capillary-like Tube Formation Assays-Tube formation by human vascular endothelial cells (HUVEC) was performed using Cultrex basement membrane extract (R&D Systems) as described (21). In some experiments, HUVEC were treated with recombinant active MMP-9 (83 kDa; EMD Chemicals, Inc.).…”

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

“…SPARC is a matricellular protein that belongs to a family of extracellular proteins that modulate cellular interactions with ECM molecules, and includes thrombspondins, tenascins, osteopontin, syndecans, and the SPARC-related proteins, SPARC like-1/hevin, testican, and SMOC-1/2 (Brekken and Sage, 2000;Sage, 2001;Rocnik et al, 2006). SPARC is highly expressed during embryogenesis and is restricted in the adult to tissues undergoing remodeling, repair, and tumorigenesis (Holland et al, 1987;Sage et al, 1989a;Bradshaw and Sage, 2001;Framson and Sage, 2004).…”