Abstract |
CXCL12 ( stromal cell-derived factor 1alpha), a ligand for CXCR4, has been shown to induce endothelial cell chemotaxis and to stimulate angiogenesis, suggesting that it may be a significant target for antiangiogenic therapy. Here we have tested suradista NSC 651016, a compound known to inhibit CXCL12-induced monocyte chemotaxis, for its ability to inhibit CXCL12-induced angiogenic activity. NSC 651016 inhibited CXCL12-mediated endothelial cell chemotaxis in a dose-dependent manner. In addition, new vessel sprouting, by both rat and chick aorta in an angiogenesis model, was inhibited. Additionally, in vitro capillary-like structure formation induced by CXCL12 was inhibited by NSC 651016. Furthermore, NSC 651016 inhibited CXCL12-mediated angiogenesis in an in vivo s.c. assay. These data indicate that suradista NSC 651016 possesses in vitro and in vivo antiangiogenic activity and has the potential to interfere with neovacularization of tumors and their metastases.
|
Authors | Gregory P Schneider, Rosalba Salcedo, Hui Fang Dong, Hynda K Kleinman, Joost J Oppenheim, O M Zack Howard |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 8
Issue 12
Pg. 3955-60
(Dec 2002)
ISSN: 1078-0432 [Print] United States |
PMID | 12473612
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- CXCL12 protein, human
- Chemokine CXCL12
- Chemokines, CXC
- NSC 651016
- Naphthalenesulfonates
|
Topics |
- Animals
- Cell Movement
(drug effects)
- Cells, Cultured
(drug effects)
- Chemokine CXCL12
- Chemokines, CXC
(antagonists & inhibitors, toxicity)
- Chemotaxis
(drug effects)
- Chickens
- Endothelium, Vascular
(drug effects, metabolism)
- Humans
- In Vitro Techniques
- Monocytes
(drug effects)
- Naphthalenesulfonates
(pharmacology)
- Neovascularization, Pathologic
(chemically induced, prevention & control)
- Rats
- Rats, Sprague-Dawley
- Stromal Cells
(drug effects, metabolism)
|