GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:19458075

From GONUTS
Jump to: navigation, search
Citation

Courtwright, A, Siamakpour-Reihani, S, Arbiser, JL, Banet, N, Hilliard, E, Fried, L, Livasy, C, Ketelsen, D, Nepal, DB, Perou, CM, Patterson, C and Klauber-Demore, N (2009) Secreted frizzle-related protein 2 stimulates angiogenesis via a calcineurin/NFAT signaling pathway. Cancer Res. 69:4621-8

Abstract

Secreted frizzle-related protein 2 (SFRP2), a modulator of Wnt signaling, has recently been found to be overexpressed in the vasculature of 85% of human breast tumors; however, its role in angiogenesis is unknown. We found that SFRP2 induced angiogenesis in the mouse Matrigel plug assay and the chick chorioallantoic membrane assay. SFRP2 inhibited hypoxia induced endothelial cell apoptosis, increased endothelial cell migration, and induced endothelial tube formation. The canonical Wnt pathway was not affected by SFRP2 in endothelial cells; however, a component of the noncanonical Wnt/Ca2+ pathway was affected by SFRP2 as shown by an increase in NFATc3 in the nuclear fraction of SFRP2-treated endothelial cells. Tacrolimus, a calcineurin inhibitor that inhibits dephosphorylation of NFAT, inhibited SFRP2-induced endothelial tube formation. Tacrolimus 3 mg/kg/d inhibited the growth of SVR angiosarcoma xenografts in mice by 46% (P = 0.04). In conclusion, SFRP2 is a novel stimulator of angiogenesis that stimulates angiogenesis via a calcineurin/NFAT pathway and may be a favorable target for the inhibition of angiogenesis in solid tumors.

Links

PubMed PMC2699405 Online version:10.1158/0008-5472.CAN-08-3402

Keywords

Animals; Calcineurin/metabolism; Calcineurin/physiology; Cell Proliferation/drug effects; Cells, Cultured; Chick Embryo; Dose-Response Relationship, Drug; Endothelial Cells/drug effects; Endothelial Cells/physiology; Female; Hemangiosarcoma/chemically induced; Hemangiosarcoma/pathology; Humans; Male; Membrane Proteins/antagonists & inhibitors; Membrane Proteins/genetics; Membrane Proteins/pharmacology; Membrane Proteins/physiology; Mice; Mice, Inbred C57BL; Mice, Nude; NFATC Transcription Factors/metabolism; NFATC Transcription Factors/physiology; Neovascularization, Pathologic/chemically induced; Neovascularization, Pathologic/genetics; Neovascularization, Pathologic/metabolism; RNA, Small Interfering/pharmacology; Signal Transduction/drug effects; Signal Transduction/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SFRP2

involved_in

GO:0001569: branching involved in blood vessel morphogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP2

involved_in

GO:0045766: positive regulation of angiogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.