Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation

Taki, Mana; Abiko, Kaoru; Baba, Tsukasa; Hamanishi, Junzo; Yamaguchi, Ken; Murakami, Ryusuke; Yamanoi, Koji; Horikawa, Naoki; Hosoe, Yuko; Nakamura, Eijiro; Sugiyama, Aiko; Mandai, Masaki; Konishi, Ikuo; Matsumura, Noriomi

doi:10.1038/s41467-018-03966-7

Cited by 223 publications

(198 citation statements)

References 36 publications

(48 reference statements)

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“…Given the reduction in CXCL2 and CCL2 expression in TLR2 KO mice, key chemoattractants for MDSCs and neutrophils versus monocytes, respectively [31][32][33], we next determined whether this would translate into impaired leukocyte recruitment. Surprisingly, no significant differences in leukocyte influx were observed in the galea or brain of TLR2 KO and WT mice at any of the time points examined (Fig.…”

Section: Resultsmentioning

confidence: 99%

TLR2 and caspase-1 signaling are critical for bacterial containment but not clearance during craniotomy-associated biofilm infection

Aldrich

Heim

Shi

et al. 2020

J Neuroinflammation

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Background: A craniotomy is required to access the brain for tumor resection or epilepsy treatment, and despite precautionary measures, infectious complications occur at a frequency of 1-3%. Approximately half of craniotomy infections are caused by Staphylococcus aureus (S. aureus) that forms a biofilm on the bone flap, which is recalcitrant to antibiotics. Our prior work in a mouse model of S. aureus craniotomy infection revealed a critical role for myeloid differentiation factor 88 (MyD88) in bacterial containment and pro-inflammatory mediator production. Since numerous receptors utilize MyD88 as a signaling adaptor, the current study examined the importance of Tolllike receptor 2 (TLR2) and TLR9 based on their ability sense S. aureus ligands, namely lipoproteins and CpG DNA motifs, respectively. We also examined the role of caspase-1 based on its known association with TLR signaling to promote IL-1β release. Methods: A mouse model of craniotomy-associated biofilm infection was used to investigate the role of TLR2, TLR9, and caspase-1 in disease progression. Wild type (WT), TLR2 knockout (KO), TLR9 KO, and caspase-1 KO mice were examined at various intervals post-infection to quantify bacterial burden, leukocyte recruitment, and inflammatory mediator production in the galea, brain, and bone flap. In addition, the role of TLR2-dependent signaling during microglial/macrophage crosstalk with myeloid-derived suppressor cells (MDSCs) was examined. Results: TLR2, but not TLR9, was important for preventing S. aureus outgrowth during craniotomy infection, as revealed by the elevated bacterial burden in the brain, galea, and bone flap of TLR2 KO mice concomitant with global reductions in proinflammatory mediator production compared to WT animals. Co-culture of MDSCs with microglia or macrophages, to model interactions in the brain vs. galea, respectively, also revealed a critical role for TLR2 in triggering pro-inflammatory mediator production. Similar to TLR2, caspase-1 KO animals also displayed increased S. aureus titers coincident with reduced pro-inflammatory mediator release, suggestive of pathway cooperativity. Treatment of caspase-1 KO mice with IL-1β microparticles significantly reduced S. aureus burden in the brain and galea compared to empty microparticles, confirming the critical role of IL-1β in limiting S. aureus outgrowth during craniotomy infection.

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Section: Resultsmentioning

confidence: 99%

TLR2 and caspase-1 signaling are critical for bacterial containment but not clearance during craniotomy-associated biofilm infection

Aldrich

Heim

Shi

et al. 2020

J Neuroinflammation

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“…GM‐CSF is an important one released by tumor cells, which can promote the proliferation of MDSCs, while G‐CSF can affect the migration of MDSCs probably by upregulating the expression of Bv8, a surface protein on MDSCs . In animal models of colorectal cancer, CXCR2 influences MDSCs migration and recruitment toward tumors by up‐regulating chemotactic factors CXCL1 and CXCL2 . CCL2 can also induce MDSCs migration to tumor site, while the deficiency of CCL2 will lead to a decline of MDSCs ratio.…”

Section: Main Functional Characteristics Of Mdscsmentioning

confidence: 99%

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Yin

Wang

et al. 2018

Intl Journal of Cancer

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Cancer progression is closely related to the tumor microenvironment in which the tumor exists, including surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules and the extracellular matrix. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can impact the growth and evolution of cancerous cells. One of major cell components in the tumor microenvironment is myeloid-derived suppressor cells (MDSCs), which promote tumor growth and metastasis directly or indirectly by recognizing other immune cells, producing cytokines and exerting their immunosuppression functions. MDSCs have emerged as major regulators of immune responses in cancer and key targets for treating cancer. There are many limitations and side-effect in approaches of conventional cancer therapy, including radiotherapy. It has grown up to be a burgeoning field that a combination of radiotherapy and immunotherapy applied to cancer therapy. Therefore, it is fundamental to explore the immune mechanism in the process of cancer treatment. Here, we reviewed the recent progress of MDSCs in roles of the tumor microenvironment and tumor radiotherapy.

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“…MDSC expansion in lymphoid organs (the spleen, bone marrow and so on), blood, and tumours has been detected in tumour-bearing mice and cancer patients 16 . MDSCs are immature myeloid cells (IMCs) that are classified into two major subsets: monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (PMN-MDSCs) 17,18 . Both have strong immunosuppressive activities but distinct functional and biochemical characteristics 19 .…”

mentioning

confidence: 99%

High-salt diet inhibits tumour growth in mice via regulating myeloid-derived suppressor cell differentiation

et al. 2020

Nat Commun

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High-salt diets are associated with an elevated risk of autoimmune diseases, and immune dysregulation plays a key role in cancer development. However, the correlation between highsalt diets (HSD) and cancer development remains unclear. Here, we report that HSD increases the local concentration of sodium chloride in tumour tissue, inducing high osmotic stress that decreases both the production of cytokines required for myeloid-derived suppressor cells (MDSCs) expansion and MDSCs accumulation in the blood, spleen, and tumour. Consequently, the two major types of MDSCs change their phenotypes: monocytic-MDSCs differentiate into antitumour macrophages, and granulocytic-MDSCs adopt pro-inflammatory functions, thereby reactivating the antitumour actions of T cells. In addition, the expression of p38 mitogen-activated protein kinase-dependent nuclear factor of activated T cells 5 is enhanced in HSD-induced M-MDSC differentiation. Collectively, our study indicates that high-salt intake inhibits tumour growth in mice by activating antitumour immune surveillance through modulating the activities of MDSCs.

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Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation

Cited by 223 publications

References 36 publications

TLR2 and caspase-1 signaling are critical for bacterial containment but not clearance during craniotomy-associated biofilm infection

TLR2 and caspase-1 signaling are critical for bacterial containment but not clearance during craniotomy-associated biofilm infection

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

High-salt diet inhibits tumour growth in mice via regulating myeloid-derived suppressor cell differentiation

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