Abstract 4892: Hypoxia enhances tumor vascularization by endothelial differentiation of endometrial cancer stem cells

Emerging evidence has shown that a small subpopulation of cancer cells plays critical roles in tumorigenesis, establishing the cancer stem cells (CSCs) theory. CSCs have properties of tumorigenesis, self-renewal and multilineage differentiation. Previous our study demonstrated that CD133+ enodometrial cancer cells showed tumorigenic and self-renewal ability, suggesting that CD133 was a potential CSC marker in endometrial cancer. In this study, we focused on multilineage differentiation and investigated an ability of endothelial differentiation in endometrial CSCs. Immunohistochemistry of subcutaneous xenografts showed that human endometrial tumors contained human vessels labeled by human-specific anti-CD31 and vWF antibodies. Endothelial tube formation assay (in vitro angiogenesis) revealed that isolated CD133+ endometrial cancer cells could show tube formation while CD133- cells could not. CD133+ cells expressed CD31 and VEGFR-1 higher than CD133- cells. In some cell types of endometrial cancer cells, flow cytometric analysis showed expression of CD31 was high ratio under hypoxia compared to normoxia. Furthermore, in vitro angiogenesis assay demonstrated hypoxic condition could promote and keep tube formation in CD133+ cells, but not CD133- cells. These results suggest that CSCs have potential of endothelial differentiation and hypoxia enhances endothelial differentiation of CSCs. These findings shed light on the establishment of new target therapy for endometrial cancer. Citation Format: Mitsuhiro Nakamura, Xiuzhi Zhang, Masahiro Takakura, Yoshiko Maida, Yasunari Mizumoto, Yukiko Bono, Toshiyuki Sasagawa, Satoru Kyo. Hypoxia enhances tumor vascularization by endothelial differentiation of endometrial cancer stem cells. [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 4892. doi:10.1158/1538-7445.AM2013-4892