Oncotarget

Research Papers:

Prostaglandin E2 produced by myeloid-derived suppressive cells induces cancer stem cells in uterine cervical cancer

Hiromasa Kuroda, Seiji Mabuchi _, Eriko Yokoi, Naoko Komura, Katsumi Kozasa, Yuri Matsumoto, Mahiru Kawano, Ryoko Takahashi, Tomoyuki Sasano, Kotaro Shimura, Michiko Kodama, Kae Hashimoto, Kenjiro Sawada, Eiichi Morii and Tadashi Kimura

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Oncotarget. 2018; 9:36317-36330. https://doi.org/10.18632/oncotarget.26347

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Abstract

Hiromasa Kuroda1,*, Seiji Mabuchi1,*, Eriko Yokoi1,*, Naoko Komura1, Katsumi Kozasa1, Yuri Matsumoto1, Mahiru Kawano1, Ryoko Takahashi1, Tomoyuki Sasano1, Kotaro Shimura1, Michiko Kodama1, Kae Hashimoto1, Kenjiro Sawada1, Eiichi Morii2 and Tadashi Kimura1

1Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan

2Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan

*These authors contributed equally to this work

Correspondence to:

Seiji Mabuchi, email: [email protected]

Keywords: MDSC; CSC; prostaglandin E2; cervical cancer; celecoxib

Received: April 13, 2018     Accepted: October 24, 2018     Published: November 20, 2018

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) enhance tumor progression by suppressing tumor-specific T cell responses, stimulating tumor angiogenesis, or promoting tumor cell metastasis. However, the biology of MDSCs have not been fully investigated. In the current study, we investigated the role of MDSCs in inducing cancer stem-like cells and explored a clinically feasible approach for targeting MDSCs-mediated cancer stem-like cells induction. In vitro and in vivo experiments revealed that MDSCs induced by tumor-derived G-CSF enhanced the stemness of cervical cancer cells by producing Prostaglandin E2 (PGE2). We also demonstrated that anti-Gr-1 neutralizing antibody or celecoxib inhibited the induction of cancer stem-like cells and enhanced the efficacy of cisplatin in cervical cancer. In clinical samples, MDSCs, PGE2, and CSCs had positive correlations. In conclusion, G-CSF-induced MDSCs enhance the stemness of uterine cervical cancer cells by producing PGE2. Targeting MDSCs or PGE2 might be a reasonable strategy for enhancing the efficacies of treatments. 


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