Abstract 2885: Retinoic acid suppressed HEY cell-induced xenograft tumor possibly through reduction of CD133+ cancer stem cells

Abstract

Abstract Ovarian cancer is the most lethal gynecologic cancer with the higher recurrence. Increasing evidence indicates that cancer stem cells plays pivotal role in tumorigenesis and chemoresistance. Retinoic acid (RA), a synthetic derivative of vitamin A, has been used for treatment and chemoprevention of ovarian cancer. But it is not clear if RA affects ovarian cancer stem cells. In this paper, we found that all-trans retinoic acid (RA) treated ovarian cancer cell HEY resulted in the significant smaller xenograft tumor in SCID/NOD mice than untreated HEY cells. To understand if RA inhibition of tumor is involved in dysfunction of cancer stem cells, we detected cancer stem cells in HEY-induced tumors. CD133 positive cells in ovarian cancer were reported to have stem-like features. We found that RA-pretreated HEY cell-induced tumors had less of CD133 positive cells (3.0%) than RA-untreated ones (5.5%). To determine if RA affects status of CD133+ cells, we first cultured HEY cells in spheroid condition. HEY cells formed spheroid in suspend culture in which the percentage of CD133+ cells was increased in analyses by flow cytometry and histochemical staining. A single spheroid of Hey cells was peritoneally injected into mice and induced ovarian tumors. Consequently, treatment of RA in initiating spheroid culture attenuated HEY spheroid formation. In analyzing the molecular mechanism of RA in tumor suppression, we found that RA-treated HEY cells increased phosphorylated PTEN and level of p53 and CRABP II, and reduced expression of CD133 in Hey cells in early period (24-48h). PTEN, a tumor suppressor gene and a PI3K functional antagonist, is widely involved in normal and cancer cell proliferation, migration, drug resistance and stem cell maintenance. We further overexpressed PTEN in HEY cells that dramatically suppressed spheroid formation, suggesting that RA-induced early PTEN activation, increases of p53 and CRABP II may be involved in change of malignancy of HEY cells. These results demonstrate that RA treatment of ovarian cancer cells would alternate the cell features that compromise the change of Cd133+ positive stem-like cells which are important in tumorigenesis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2885.