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- W84949068 abstract "Abstract : Angiogenesis is the growth of new capillary blood vessels, and is a critical component of solid tumor growth. We characterized molecular changes between human breast tumor vessels and normal vessels to identify genes that may serve as therapeutic targets. We developed a method for rapid immunohistochemistry (IHC) and laser capture microdissection (LCM) of vascular cells from frozen human breast tumors and normal breast tissue for genomic analysis. We found SFRP2 to have 6 fold increased mRNA expression in breast tumor vessels, and confirmed localization of SFRP2 to endothelium using IHC with antibodies to SFRP2 on paraffin-embedded breast tumors. SFRP2 protein expression in endothelium was significantly higher in breast tumors than normal (13/15 or 87% versus 4/10 or 40%, p=0.03). We found that SFRP2 stimulates angiogenesis ex vivo and in vitro through a calcineurin/ NFAT pathway. A polyclonal antibody to SFRP2 inhibited malignant endothelial tube formation, demonstrating the contribution of SFRP2 to angiogenesis. We found that tacrolimus, a calcineurin/ NFAT inhibitor inhibits SFRP2 induced endothelial tube formation, and inhibited malignant endothelial tumor growth in mice. Based on its expression and function, we have discovered that SFRP2 is a novel therapeutic target for the treatment of breast cancer." @default.
- W84949068 created "2016-06-24" @default.
- W84949068 creator A5034923308 @default.
- W84949068 date "2008-05-01" @default.
- W84949068 modified "2023-09-23" @default.
- W84949068 title "Characterization of Gene Expression in Human Breast Tumor Endothelium" @default.
- W84949068 doi "https://doi.org/10.21236/ada486849" @default.
- W84949068 hasPublicationYear "2008" @default.
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