Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 404, Issue 1, Pages 86-89Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.11.069
Keywords
Heparan sulfate; Angiogenesis; Xyloside; Proteoglycan; Inhibitor; Matrigel
Categories
Funding
- National Institutes of Health [GM075168]
- Human Frontier Science Program
- American Heart Association
- Vietnam Education Foundation
- Grants-in-Aid for Scientific Research [23590005] Funding Source: KAKEN
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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. (C) 2010 Elsevier Inc. All rights reserved.
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