IL-6 restores dendritic cell maturation inhibited by tumor-derived TGF-β through interfering Smad 2/3 nuclear translocation

Lin, Chen-Si; Chen, Mo-Fan; Wang, Yushan; Chuang, Tung‐Han; Chiang, Yi-Lun; Chu, Ruiai

doi:10.1016/j.cyto.2013.03.005

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…By affecting SMAD proteins' entry into the nucleus, players such as miR-26a, IL-6 (interleukin-6), and HSP72 can block the downstream signaling events of TGF-β by inhibiting the nuclear translocation of phosphorylated SMAD proteins [140][141][142]. Another example is PCDHGA9, a member of the cadherin family that inhibits not only the phosphorylation of SMAD2/3 but also the nuclear translocation of pSMAD2/3, inhibiting downstream signaling events of TGF-β through a dual-action.…”

Section: Regulatory Mechanisms Beyond Posttranslationalmentioning

confidence: 99%

The Role of TGF-β Signaling Pathways in Cancer and Its Potential as a Therapeutic Target

Yang

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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The transforming growth factor-β (TGF-β) signaling pathway mediates various biological functions, and its dysregulation is closely related to the occurrence of malignant tumors. However, the role of TGF-β signaling in tumorigenesis and development is complex and contradictory. On the one hand, TGF-β signaling can exert antitumor effects by inhibiting proliferation or inducing apoptosis of cancer cells. On the other hand, TGF-β signaling may mediate oncogene effects by promoting metastasis, angiogenesis, and immune escape. This review summarizes the recent findings on molecular mechanisms of TGF-β signaling. Specifically, this review evaluates TGF-β′s therapeutic potential as a target by the following perspectives: ligands, receptors, and downstream signaling. We hope this review can trigger new ideas to improve the current clinical strategies to treat tumors related to the TGF-β signaling pathway.

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Section: Regulatory Mechanisms Beyond Posttranslationalmentioning

confidence: 99%

The Role of TGF-β Signaling Pathways in Cancer and Its Potential as a Therapeutic Target

Yang

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…The IL-6 is a cytokine that acts as both a proinflammatory and an (Lin et al, 2013;Park et al, 2004). In this study, the increased expression level of IL-6 was observed in DCs after coculture with overexpressed Let-7i and miR-155 exosomes but it was notably more in TEX-m155 group and it may have influence on maintaining inactive DCs.…”

Section: Discussionmentioning

confidence: 51%

“…It has been reported that enhanced levels of IL‐6 could neutralize TGF‐β expression on DCs. Though, IL‐6 plays a major role in maintaining immature DC (Lin et al, ; Park et al, ). In this study, the increased expression level of IL‐6 was observed in DCs after coculture with overexpressed Let‐7i and miR‐155 exosomes but it was notably more in TEX‐m155 group and it may have influence on maintaining inactive DCs.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, the increased expression level of IL‐6 was observed in DCs after coculture with overexpressed Let‐7i and miR‐155 exosomes but it was notably more in TEX‐m155 group and it may have influence on maintaining inactive DCs. TGF‐β was downregulated by Let‐7i that may be related to IL‐6 expression levels which affected TGF‐β expression and also it would be miRNAs direct effect (Lin et al, ). Moreover, IL‐1b upregulation in our experiments showed that Let‐7i could modulate IL‐1 signaling pathway that was proved in activated human monocyte‐derived DC (Ceppi et al, ).…”

Section: Discussionmentioning

confidence: 99%

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microRNA modified tumor‐derived exosomes as novel tools for maturation of dendritic cells

Khani

Hassan

Ebrahimi

et al. 2018

Journal Cellular Physiology

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Tumor‐derived exosomes (TEX) are known by their immune suppression effects as well as initiation mediators in cancer progression and metastasis. Meanwhile, they are appropriate sources to induce immunity against tumor cells, as consist of tumor specific and associated antigens. The aim of the current study is modifying TEX with microRNA miR‐155, miR‐142, and let‐7i, to enhance their immune stimulation ability and induce potent dendritic cells (DC). For this, exosomes were isolated from mouse mammalian breast cancer cell line; 4T1, and subjected to miR‐155, miR‐142, and let‐7i by electroporation. Immature DCs were generated from mouse bone marrow in the presence of interleukin‐4 (IL‐4) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). To mature DCs, lipopolysaccharide (LPS), TEX, and modified TEX were used. The expression level of miRNAs and their target genes (IL‐6, IL‐17, IL‐1b, TGFβ, SOCS1, KLRK1, IFNγ, and TLR4) was determined. TEX were nanovesicles with spheroid morphology which expressed CD81, CD63, and TSG101, as exosome markers, at protein level. MHCII, CD80, and CD40 as maturation markers were assessed by flow cytometry. Overexpression of miRNAs were confirmed in exosomes and mDCs. Up and downregulation of target genes confirmed the gene network in DC maturation. We found that Let‐7i could efficiently induce the DC maturation, as well as miR‐142 and miR‐155 have enhancing effects. These findings reveal that the modified TEX would be a hopeful cell‐free vaccine for the cancer treatment.

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“…at the indicated concentrations for various periods of time were prepared for immunoblotting of LC3, p53, Caspase 3, Bcl2, Bcl2-associated X protein (Genetex, USA). Western blot analysis was performed as previously reported [29]. The original blots can be referred in the additional file 1.…”

Section: Western Blottingmentioning

confidence: 99%

Inhibiting autophagy potentiates the antitumor efficacy of Euphorbia royleana for canine mammary gland tumors

et al. 2020

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Background: Canine mammary gland tumors (cMGTs) are the most common neoplasms in intact female canines and viewed as a suitable model for studying human breast cancers. Euphorbia royleana has been reported to have a variety of antitumor efficacies. We have prepared the crude extracts of E. royleana in ethanol and hexane solvents to evaluate the anti-tumor effects for cMGT in vitro and in vivo. Results: The results showed that E. royleana could inhibit cell proliferation and colony formation in cMGT cells. The suppression of tumor cell growth resulted from necrosis and cell cycle arrest. Moreover, autophagy appears to play a critical role in E. royleana-mediated cell death by triggering cell apoptosis. The in vivo results also revealed that E. royleana treatment could reduce the size of solid tumors while exhibiting low toxicity in cMGT-bearing nude mice. Conclusions: The anti-tumor mechanisms of E. royleana were firstly verified to show it would cause autophagic cell death, apoptosis, and cell cycle arrest in canine mammary tumor cells. The in vitro and in vivo findings in the present study revealed E. royleana has potential anticancer effects for the treatment of canine mammary gland tumors.

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IL-6 restores dendritic cell maturation inhibited by tumor-derived TGF-β through interfering Smad 2/3 nuclear translocation

Cited by 10 publications

References 40 publications

The Role of TGF-β Signaling Pathways in Cancer and Its Potential as a Therapeutic Target

The Role of TGF-β Signaling Pathways in Cancer and Its Potential as a Therapeutic Target

microRNA modified tumor‐derived exosomes as novel tools for maturation of dendritic cells

Inhibiting autophagy potentiates the antitumor efficacy of Euphorbia royleana for canine mammary gland tumors

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