Cancer stem cells (CSC) are closely associated with tumor vasculature in the CSC niche. Tumor vascular cells are known to provide critical growth, differentiation, and survival cues for CSC. Unfortunately little is known about the specific factors produced by vascular cells. EGFL6 is a factor specifically secreted by ovarian tumor vascular cells. EGFL6 is reported to regulate the differentiation of normal stem cells. We examined the impact of EGFL6 on ovarian cancer cell growth. We found that EGFL6 significantly promoted ovarian cancer cell growth in vitro. Ovarian cancer cell proliferation was associated with a decrease in the percentage of ALDH+ ovarian CSC. Using a novel single cell microfluidic culture system we found that EGFL6 acts specifically on ALDH+ CSC to promote proliferation via asymmetric division. We used a in vivo novel model of human tumor vasculature to express EGFL6 in vivo and demonstrate that EGFL6 significantly promotes ovarian tumor growth. Finally we generated an EGFL6 blocking antibody and found that anti-EGFL6 antibodies could restrict tumor growth and delay disease recurrences. Thus EGFL6 is an import vascular regulator of ovarian CSC and EGL6 blocking antibodies represent a potentially important ovarian CSC targeting therapeutic.

Citation Format: Ronald J. Buckanovich, Shoumei Bai, Ning Deng, Patrick Ingram, Euisik Yoon. EGFL6 is a tumor vascular regulator of ovarian CSC asymmetric division and a novel therapeutic target. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3760. doi:10.1158/1538-7445.AM2013-3760