Inhibiting MDSC differentiation from bone marrow with phytochemical polyacetylenes drastically impairs tumor metastasis

Wei, Wen‐Chi; Lin, Sheng-Yen; Lan, Chun-Wen; Huang, Yu‐Chen; Lin, Chih‐Yu; Hsiao, Pei-Wen; Chen, Yet-Ran; Yang, Wen‐Chin; Yang, Ning‐Sun

doi:10.1038/srep36663

Cited by 26 publications

(21 citation statements)

References 49 publications

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“…Bone marrow is rich in mononuclear cells containing CD11b+Gr-1+ cells. Various research has indicated that bone marrow is the major source of CD11b+Gr-1+ cells [23]. However, the spleen contains numerous monocytes or promonocytes.…”

Section: Discussionmentioning

confidence: 99%

The Mobilization of Splenic Reservoir Myeloid-Derived Suppressor Cells in Sepsis-Induced Myocardial Injury

Fu¹,

Xu²,

Tang³

et al. 2019

Preprint

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Background Myeloid-derived suppressor cells (MDSCs) play key roles in sepsis, but whether bone marrow is considered the only source remains unclear. The current knowledge about the mechanism of MDSCs leading to myocardial injury in sepsis is poor. Methods In sepsis patients with cardiac dysfunction, the circulating percentage of CD14-CD11b+ and serum concentrations of IL-6 and IL-1β were measured. A mouse sepsis model was established through caecum ligation and puncture (CLP). Animals were divided into four groups: control, sham, CLP and CLP+splenectomy (CLPS). Plasma concentrations of IL-6, IL-1β, TnI and NT-proBNP were measured. CD11b+Gr-1+ cells were detected by immunofluorescence staining and RT-PCR. Myocardial injury was detected by HE, Masson and TUNEL staining. The expression of mTOR, P53 and caspase-3 was measured by Western blot. Results In sepsis patients, circulating MDSCs were increased, and the plasma concentrations of IL-6 and IL-1β were elevated. The plasma concentrations of IL-6 and IL-1β were correlated with the ratio of circulating MDSCs. In the mouse sepsis model, the spleen was the major source of CD11b+Gr-1+ cells that migrated into circulation and the heart in sepsis. The serum concentrations of IL-6 and IL-1β were also elevated. Echocardiography and serum biomarkers showed that cardiomyocyte damage and cardiac hypofunction in sepsis induced myocardial imjury. The expression of CD11b, Gr-1 and pro-inflammatory cytokines in the heart was significantly higher in sepsis patients than that in controls. Pathological staining and TUNEL staining showed obvious myocardial damage and cell apoptosis. The Western blot analysis indicated that in the heart, the activation of mTOR was inhibited and that the expression of P53 and caspase-3 was elevated in sepsis-induced myocardial injury. Conclusion In sepsis-induced myocardial injury, splenic reservoir CD11b+Gr-1+ cells rapidly migrated into circulation and the heart, further impairing heart function via the high expression of P53 through the inhibition of mTOR.

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Section: Discussionmentioning

confidence: 99%

The Mobilization of Splenic Reservoir Myeloid-Derived Suppressor Cells in Sepsis-Induced Myocardial Injury

Fu¹,

Xu²,

Tang³

et al. 2019

Preprint

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“…MDSCs have now been categorized into two distinctive subtypes. These are the monocytic MDSCs and granulocytic MDSCs (M-MDSCs and G-MDSCs) [3].…”

Section: Introductionmentioning

confidence: 99%

“…This factor is principally required for the differentiation of M-MDSCs. Also, tumor-derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) has demonstrated to partake in M-MDSC generation [3,6]. Nevertheless, the proportion of G-MDSC to M-MDSC in diverse cancer models is extremely unpredictable and relies on factors that still need further investigation into.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have evidenced that MDSCs involve dual healing target due to their essential immunomodulatory tasks such as elimination or suppression of hypothetically positive immune response, as seen in tumor or cancer immunotherapy and expansion of endogenous MDSCs seen in conditions in which alteration of the immune responses is advantageous as in the therapy of graft versus host disease or autoimmunity [1,8]. It has also been postulated that immature MDSCs infiltrates into a particular cancer microenvironment and can differentiate into Tumor-Associated Macrophages (TAM) [3,9]. Therefore, numerous MDSCs has proven to partake in cancer-triggered immunosuppressive actions.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, numerous MDSCs has proven to partake in cancer-triggered immunosuppressive actions. On the other hand, averting the expansion of MDSCs is being investigated as an auspicious modality of combating various cancers [3].…”

Section: Introductionmentioning

confidence: 99%

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Myeloid-derived Suppressor Cells in Cancer: A Review on the Pathogenesis and Therapeutic Potentials

Richard¹

2018

TOCIJ

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Myeloid-Derived Suppressor Cells (MDSCs) are multifarious group of immature cells that arise from the myeloid and amass in individuals with cancer, sepsis, burns, or chronic inflammation. It has been evidenced that these group of cells are efficient in modifying adaptive and innate immune responses, coherent with their assumed key biological roles. It is evidenced that MDSCs inter-communicate with Tumor-Associated Macrophages (TAM), Tumor-Associated Neutrophils (TAN), Dendritic Cells (DCs), Receptor for Advanced Glycation End-products (RAGE), Toll-Like Receptors (TLRs), Matrix Metalloproteinase (MMPs) as well as High Mobility Group Box 1 (HMGB1) during carcinogenesis. This interaction although elaborated in various studies and reviews still does not explain in details as to how their interplay results in cancer pathogenesis. We noted that MDSC contributed to cancer immune suppressionviaTLR-4 receptor and lipopolysaccharideas (LPS). Furthermore, MDSC contributed to cancer developmentviaMMPs (MMP-9 and MMP1-12) as well as RAGE. In the cancer microenvironment, HMGB1-driven MDSC amassment expedites cancer development and metastasisviaPMN-MDSCs, macrophages, DCs and Immature Myeloid Cells (IMC). Also, HMGB1 intermediation with MDSCsviaRAGE and/or TLR-4 leading to cancer development. Nevertheless, MDSCs have already proven potent in some cancers and are currently been used as treatment options although further studies are needed in some other cancers. Our review, therefore, explores the pivotal pathogenic and therapeutic roles of MDSCs in cancer.

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Polyacetylene Glycosides: Isolation, Biological Activities and Synthesis

Santos

Filho

et al. 2021

The Chemical Record

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Polyacetylene glycosides (PAGs) constitute a relatively small class of secondary metabolites characterized by the presence of a sugar unit anomerically connected to a polyacetylene. These compounds are found in fungi, seaweed, and more often in plants. PAGs exhibit a wide range of biological and pharmacological activities and, as a result, the literature of these compounds has grown exponentially in recent years.

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Inhibiting MDSC differentiation from bone marrow with phytochemical polyacetylenes drastically impairs tumor metastasis

Cited by 26 publications

References 49 publications

The Mobilization of Splenic Reservoir Myeloid-Derived Suppressor Cells in Sepsis-Induced Myocardial Injury

The Mobilization of Splenic Reservoir Myeloid-Derived Suppressor Cells in Sepsis-Induced Myocardial Injury

Myeloid-derived Suppressor Cells in Cancer: A Review on the Pathogenesis and Therapeutic Potentials

Polyacetylene Glycosides: Isolation, Biological Activities and Synthesis

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