Abstract 1416: Granulocyte-colony stimulating factor (G-CSF) enhances stemness by inducing myeloid-derived suppressor cell (MDSC) in cervical cancer

Abstract

Abstract Objectives: Granulocyte-colony stimulating factor (G-CSF) is known to induce the myeloid-derived suppressor cell (MDSC) to stimulate the progression of uterine cervical cancer. The aim of the current study is to investigate the role of MDSC in the induction of cancer stem cells in uterine cervical cancer. Methods: We first established cervical cancer cell lines stably transfected with G-CSF expression vector (ME180-GCSF) or control vector (ME180-control). Then, using BALB/c nude mice subcutaneously inoculated with ME180-G-CSF or ME180-control cells, the effect of G-CSF on the induction of MDSCs (CD11b+Gr1+ cells) and cancer stem cells (ALDH-high cells) were assessed by flow cytometry. Using MDSCs isolated from the spleens of ME180-GCSF-bearing mice, we next investigated whether the MDSCs induce cancer stem cells in vitro. Finally, we analyzed the association between the G-CSF expression and ALDH1A1 expression in human cervical cancer specimens by immunohistochemistry. Results: 1) G-CSF induces MDSCs from mice bone marrow. 2) ME180-GCSF-derived tumors contain greater number of MDSCs and ALDH-high cells. 3) Co-incubation of ME180 with MDSCs cells increased the number of ALDH-high cells. 4) A positive correlation was observed between the tumor G-CSF expression and ALDH1A1 expression in human cervical cancers. Conclusions: G-CSF-induced MDSCs increase the number of cancer stem cells in uterine cervical cancer. Citation Format: Hiromasa Kuroda. Granulocyte-colony stimulating factor (G-CSF) enhances stemness by inducing myeloid-derived suppressor cell (MDSC) in cervical cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1416. doi:10.1158/1538-7445.AM2015-1416