Secreted frizzle-related protein 2 stimulates angiogenesis via a calcineurin/NFAT signaling pathway.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Courtwright, A; Siamakpour-Reihani, S; Arbiser, JL; Banet, N; Hilliard, E; Fried, L; Livasy, C; Ketelsen, D; Nepal, DB; Perou, CM; Patterson, C; Klauber-Demore, N

Published Date

  • June 2009

Published In

Volume / Issue

  • 69 / 11

Start / End Page

  • 4621 - 4628

PubMed ID

  • 19458075

Pubmed Central ID

  • 19458075

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-08-3402

Language

  • eng