Characterization of Gene Expression in Human Breast Tumor Endothelium
Annual summary rept. 1 May 2007-30 Apr 2008
NORTH CAROLINA UNIV AT CHAPEL HILL
Pagination or Media Count:
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 1315 or 87 versus 410 or 40, p0.03. 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.
- Anatomy and Physiology
- Medicine and Medical Research