Their abstract, titled, “A Monoclonal Antibody to SFRP2 Inhibits Triple-Negative Breast Tumor Growth in vivo,” described their findings about a protein named SFRP2.
This protein was thought to be a tumor suppressor by inhibiting activation of a protein named ß-catenin. What the UNC group reported was that SFRP2, instead of functioning as a tumor suppressor, actually promotes angiogenesis, the process by which tumors grow blood vessels to fuel their spread.
They tested their hypothesis in breast cancer and murine cell lines and determined that SFRP2 increased ß-catenin in both cell lines. Additionally SFRP2 increases the NFAT protein in endothelial cells, the main type of cell found in the inside lining of blood vessels. NFAT is involved in inducing angiogenesis.
They then tested their hypothesis in pre-clinical models and triple-negative breast cancer cell lines. Triple-negative beast cancer is estrogen, progesterone, and HER2 receptor negative. Tumors were treated with a buffer control, the antiangiogenic agent bevacizumab (Avastin), or an anti-SFRP2 monoclonal antibody.
They reported that treatment with the anti-SFRP2 monoclonal antibody resulted in significant tumor reduction (54 percent) while bevacizumab treatment resulted in a 32 percent reduction, whixh was not statistically significant. This study is their second demonstrating the antiangiogenic effect of the SFRP2 monoclonal antibody. (Their first pre-clinical study demonstrated that the SFRP2 monoclonal antibody inhibits the growth of angiosarcomas, a rare cancer of blood vessels.)
They conclude that “the anti-SFRP2 monoclonal antibody resulted in a reduction in breast tumor growth in tumors that were not sensitive to Avastin. This finding suggests that SFRP2 is a therapeutic target for breast cancer.” Future studies are planned. Co-authors Drs. Demore and Cam Patterson have co-founded Enci Therapeutics, Inc., to support the clinical development of a monoclonal antibody to SFRP2 for cancer.
Other UNC authors are Emily Fontenot, MD; Russ Mumper, PhD; XJ Shen, PhD; Shara Siamakpour Reihani, PhD; Eleanor Hilliard, BS; Bradley Bone, BS; David Ketelson, BS; Charlene Ross, BS; and Emma Rossi, MD.