Abstract 5199: Tumor vascularization by endothelial differentiation of endometrial cancer stem cells

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Evidence for existence of cancer stem cells (CSCs) has been reported in several malignant tumors. CSCs have properties of self-renewal, tumorigenesis and multilineage differentiation. Many studies about CSCs have focused on self-renewal, tumorigenesis. However, it is unclear about multilineage differentiation. Our previous study showed CD133 was a CSC marker and a critical prognostic marker in endometrial cancer. In that study, we demonstrated that CD133+ cells were capable of generating both CD133+ and CD133- cells, whereas CD133 cells did not generate CD133+ cells, indicating that CD133+ CSCs have a differential ability. The present study investigated endothelial differentiation of endometrial cancer cells. We have established endometrial cancer cells from normal human endometrial epithelial cells by introduction of HPV16 E6/E7, hTERT and K-ras genes (EM-E6/E7/hTERT/K-ras cells). Histological findings of tumors formed from EM-E6/E7/hTERT/K-ras cells showed that tumors were composed of solid and vascular regions. Vascular regions were stained human-specific anti-CD31 antibody, suggesting that EM-E6/E7/hTERT/K-Ras cells are capable of differentiating to endothelial cells. Subcutaneous xenografts from clinical samples in endometrial cancer also demonstrated that human endometrial tumors contained human vessels labeled by human-specific anti-CD31 antibody. Endothelial tube formation assay (in vitro angiogenesis) revealed that isolated CD133+ endometrial cancer cells could show tube formation while CD133- cells could not, indicating that CD133+ endometrial cancer cells had an ability of endothelial differentiation. Furthermore, western blot analysis showed high expression of VEGFR1 in CD133+ cells. We demonstrated a new function of CSCs in endometrial cancer cells. These findings shed light on the establishment of new target therapy to endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5199. doi:1538-7445.AM2012-5199