The role of MMP-9 in the anti-angiogenic effect of secreted protein acidic and rich in cysteine

Abstract

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), a matricellular glycoprotein, modulates cellular interaction with the extracellular matrix and is capable of altering the growth of various cancers. We therefore sought to determine the effect of SPARC expression on medulloblastoma tumour growth and angiogenesis. METHODS: To this extent, we selected three SPARC full-length cDNA overexpressed clones (Daoy-SP). Consequences of SPARC overexpression were studied in terms of cell growth, angiogenesis using co-culture assay in vitro, dorsal skin-fold chamber assay in vivo, PCR Array for human angiogenic genes, as well as western blotting for angiogenic molecules and tumour growth, in an orthotopic tumour model. RESULTS: The SPARC protein and mRNA levels were increased by approximately three-fold in Daoy-SP cells compared with parental (Daoy-P) and vector (Daoy-EV) controls. Daoy-SP clones reduced tumour cell-induced angiogenesis in vitro and in vivo, and formed small tumours with fewer blood vessels when compared with controls. Matrix metalloprotease-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression were decreased in Daoy-SP clones. Further, inhibition of MMP-9 expression caused SPARCmediated inhibition of angiogenesis and tumour growth as MMP-9 rescued SPARC-mediated anti-angiogenic effect in vitro and tumour growth inhibition in vivo. CONCLUSION: Overexpression of SPARC decreases angiogenesis, which leads to decreased tumour growth. Further, the role of MMP-9 could be attributed to the anti-angiogenic effect of SPARC.

New 4-Maleamic Acid and 4-Maleamide Peptidyl Chalcones as Potential Multitarget Drugs for Human Prostate Cancer

“…Our results showed that our chalcones also inhibited angiogenesis according to the chick embryo CAM model, suggesting the potential antiangiogenic effect of these structures, as previously shown with the 2-hydroxy-4-methoxy chalcone via the blockade of the vascular endothelial growth factor receptor signal pathway (26,38). The effect of the chalcones on MMP-9 could also be responsible for this inhibition of angiogenesis (39).…”

Overexpression of SPARC in Human Trabecular Meshwork Increases Intraocular Pressure and Alters Extracellular Matrix

“…58 In tumor cells, SPARC overexpression resulted in a decrease in pro-MMP-9. 59 Other groups have examined the effects of SPARC suppression. Tumors grown in SPARC-null mice exhibited reduced deposition of fibrillar collagen types I and III, basement membrane collagen IV, and the collagen-associated proteoglycan decorin.…”

Nuclear Translocation of Hand-1 Acts as a Molecular Switch to Regulate Vascular Radiosensitivity in Medulloblastoma Tumors: The Protein uPAR Is a Cytoplasmic Sequestration Factor for Hand-1

“…The implantation technique of the dorsal skin-fold chamber model has been described previously (34). Briefly, diffusion chambers with control-, Hand-1OE-, or FL-uPAR-transfected stable cells (2 Â 10 6 ) were placed subcutaneously in the skin through the superficial incision made horizontally along the edge of the dorsal air sac.…”