title: Novel glycosaminoglycan biosynthetic inhibitors affect tumor-associated angiogenesis.
abstract: Heparan sulfate proteoglycans (HSPGs) are essential players in several steps of tumor-associated angiogenesis. As co-receptors for several pro-angiogenic factors such as VEGF and FGF, HSPGs regulate receptor-ligand interactions and play a vital role in signal transduction. Previously, we have employed an enzymatic strategy to show the importance of cell surface HSPGs in endothelial tube formation in vitro. We have recently found several fluoro-xylosides that can selectively inhibit proteoglycan synthesis in endothelial cells. The current study demonstrates that these fluoro-xylosides are effective inhibitors of endothelial tube formation in vitro using a matrigel based assay to simulate tumor-associated angiogenesis. These first generation scaffolds offer a promising stepping-stone to the discovery of more potent fluoro-xylosides that can effectively neutralize tumor growth.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Raman
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Thao Kim Nu
authors.initials: TK
authors.lastname: Nguyen
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuzuki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
authors.forename: Balagurunathan
authors.initials: B
authors.lastname: Kuberan
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D019812:Heparan Sulfate Proteoglycans / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D006027:Glycosides; D019812:Heparan Sulfate Proteoglycans; C010807:xylosides