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

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

doi:10.18632/oncotarget.26347

Cited by 54 publications

(39 citation statements)

References 39 publications

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“…Sphere formation assay was conducted as reported previously. 22 Endometrial cancer cells (Ishikawa or Hec1B cells) were plated in ultra-low attachment surface 6-well plates with serum-free medium supplemented with basic fibroblast growth factor (10 ng/ml; ReproCELL, Inc., Kanagawa, Japan), epithelial growth factor (20 ng/ml; R&D Systems), and B27 supplement. After 2 weeks, the number of spheres in each well was counted using a phase-contrast microscope.…”

Section: Sphere Formation Assaymentioning

confidence: 99%

“…The ALDH1 immunoreactivity in tumor cells was assessed using an immunoreactive score according to Remmele and Stegner (IRS). 22 Enzyme-linked immunosorbent assay (ELISA)…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…When Ishikawa cells were co-cultured with MDSCs extracted from the spleens of Ishikawa-G-CSF-derived tumor-bearing mice, the frequency of ALDH-high Ishikawa cells was significantly increased (Figure 3(a)). Because PGE2, a mediator of inflammation, has recently been reported to enhance the stemness of cervical, colorectal, or bladder cancer cells, 22,28,29 we examined whether PGE2 can enhance the stemness of endometrial cancer cells. As shown in Figure 3(b) and Figure S4A, both Ishikawa and Hec1B cells expressed EP2 and EP4 receptors, which are known to be involved in PGE2 signaling.…”

Section: Role Of G-csf-induced Mdscs and Mdsc-derived Pge2 In The Indmentioning

confidence: 99%

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The role of myeloid-derived suppressor cells in endometrial cancer displaying systemic inflammatory response: clinical and preclinical investigations

et al. 2019

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Systemic inflammatory responses including thrombocytosis, leukocytosis, or neutrophilia have gained attention as prognostic indicators in patients with various solid malignancies.current study, we aimed to investigate the clinical implications and underlying biological mechanism of the systemic inflammatory response in endometrial cancer. Clinical data from 900 patients with endometrial cancer were analyzed to investigate the association between pretreatment leukocytosis, thrombocytosis, and treatment outcome. Clinical samples, endometrial cancer cell lines, and a mouse model of endometrial cancer were used to examine the mechanisms responsible for systemic inflammatory response in endometrial cancer, focusing on the role of tumor-derived granulocyte colony-stimulating factor (G-CSF) and MDSCs. Then, we showed that pretreatment concurrent leukocytosis and thrombocytosis is associated with significantly shorter survival and decreased chemosensitivity among patients with endometrial cancer. In vitro and in vivo experiments revealed that tumor-derived G-CSF and G-CSF-mediated IL-6 production from the tumor microenvironment are involved in the development of leukocytosis and thrombocytosis in patients with endometrial cancer. Moreover, increased tumor-infiltrating MDSCs induced by tumorderived G-CSF, MDSC-mediated T cell suppression, and MDSC-mediated cancer stem cell induction are responsible for progression and chemoresistance in this type of endometrial cancer. MDSC depletion using an anti-Gr-1 neutralizing antibody or inhibition of MDSC activity by celecoxib inhibited tumor growth and enhanced chemosensitivity in endometrial cancer displaying concurrent leukocytosis and thrombocytosis. In conclusion, Pretreatment concurrent leukocytosis and thrombocytosis are associated with significantly shorter survival and decreased chemosensitivity among patients with endometrial cancer. Combining MDSC-targeting treatments with current standard chemotherapies might have therapeutic efficacy for these patients.

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Section: Sphere Formation Assaymentioning

confidence: 99%

“…The ALDH1 immunoreactivity in tumor cells was assessed using an immunoreactive score according to Remmele and Stegner (IRS). 22 Enzyme-linked immunosorbent assay (ELISA)…”

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Role Of G-csf-induced Mdscs and Mdsc-derived Pge2 In The Indmentioning

confidence: 99%

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The role of myeloid-derived suppressor cells in endometrial cancer displaying systemic inflammatory response: clinical and preclinical investigations

et al. 2019

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“…They can block the IFN-γ production by NK cells by affecting Stat5 activity and reducing NKG2D expression by NK cells through cell–cell interactions, leading to the suppression of NK cell cytotoxicity in tumor-bearing mice [ 193 , 194 ]. The production of PGE2 by MDSC was shown to enhance the stemness of uterine cervical cancer and the promotion of PD-L1 expression in epithelial ovarian cancer [ 195 , 196 ].…”

Section: Mdscmentioning

confidence: 99%

Cancer Cells Resistance Shaping by Tumor Infiltrating Myeloid Cells

Domagala

Laplagne

Leveque

et al. 2021

Cancers

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Interactions between malignant cells and neighboring stromal and immune cells profoundly shape cancer progression. New forms of therapies targeting these cells have revolutionized the treatment of cancer. However, in order to specifically address each population, it was essential to identify and understand their individual roles in interaction between malignant cells, and the formation of the tumor microenvironment (TME). In this review, we focus on the myeloid cell compartment, a prominent, and heterogeneous group populating TME, which can initially exert an anti-tumoral effect, but with time actively participate in disease progression. Macrophages, dendritic cells, neutrophils, myeloid-derived suppressor cells, mast cells, eosinophils, and basophils act alone or in concert to shape tumor cells resistance through cellular interaction and/or release of soluble factors favoring survival, proliferation, and migration of tumor cells, but also immune-escape and therapy resistance.

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“…8 PGE 2 secreted from myeloid-derived suppressive cells might also induce cervical CSC formation and expansion in vitro. 9 Moreover, PGE 2 has been shown to induce colonic CSC expansion by activating NF-κB via EP4-PI3K and EP4-MAPK signaling and promote liver metastases in an orthotopic mouse model of metastatic CRC. 10 In CRC cell lines, PGE 2 induced YAP1 expression and transcriptional activity, which resulted in induction of both COX-2 and EP4 gene transcription.…”

mentioning

confidence: 99%