Dataset Information

MiR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis.

ABSTRACT: The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We report here that miR-126/miR-126(*), a microRNA pair derived from a single precursor, independently suppress the sequential recruitment of mesenchymal stem cells and inflammatory monocytes into the tumour stroma to inhibit lung metastasis by breast tumour cells in a mouse xenograft model. miR-126/miR-126(*) directly inhibit stromal cell-derived factor-1 alpha (SDF-1?) expression, and indirectly suppress the expression of chemokine (C-C motif) ligand 2 (Ccl2) by cancer cells in an SDF-1?-dependent manner. miR-126/miR-126(*) expression is downregulated in cancer cells by promoter methylation of their host gene Egfl7. These findings determine how this microRNA pair alters the composition of the primary tumour microenvironment to favour breast cancer metastasis, and demonstrate a correlation between miR-126/126(*) downregulation and poor metastasis-free survival of breast cancer patients.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC3672398 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis.

Zhang Yun Y Yang Pengyuan P Sun Tao T Li Dong D Xu Xin X Rui Yaocheng Y Li Chaoran C Chong Mengyang M Ibrahim Toni T Mercatali Laura L Amadori Dino D Lu Xincheng X Xie Dong D Li Qi-Jing QJ Wang Xiao-Fan XF

Nature cell biology 20130210 3

The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We report here that miR-126/miR-126(*), a microRNA pair derived from a single precursor, independently suppress the sequential recruitment of mesenchymal stem cells and inflammatory monocytes into the tumour stroma to inhibit lung metastasis by breast ...[more]

PMID: 23396050

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Project description:Microglia are the primary immunocompetent cells in brain tissue and microglia-mediated inflammation is associated with the pathogenesis of various neuronal disorders. Recently, many studies have shown that mesenchymal stem cells (MSCs) display a remarkable ability to modulate inflammatory and immune responses through the release of a variety of bioactive molecules, thereby protecting the central nervous system. Previously, we reported that MSCs have the ability to modulate inflammatory responses in a traumatic brain injury model and that the potential mechanisms may be partially attributed to upregulated TNF-? stimulated gene/protein 6 (TSG-6) expression. However, whether TSG-6 exerts an anti-inflammatory effect by affecting microglia is not fully understood. In this study, we investigated the anti-inflammatory effects of MSCs and TSG-6 in an in vitro lipopolysaccharide (LPS)-induced BV2 microglial activation model. We found that MSCs and TSG-6 significantly inhibited the expression of pro-inflammatory mediators in activated microglia. However, MSC effects on microglia were attenuated when TSG-6 expression was silenced. In addition, we found that the activation of nuclear factor (NF)-?B and mitogen-activated protein kinase (MAPK) pathways in LPS-stimulated BV2 microglial cells was significantly inhibited by TSG-6. Furthermore, we found that the presence of CD44 in BV2 microglial cells was essential for MSC- and TSG-6-mediated inhibition of pro-inflammatory gene expression and of NF-?B and MAPK activation in BV2 microglial cells. The results of this study suggest that MSCs can modulate microglia activation through TSG-6 and that TSG-6 attenuates the inflammatory cascade in activated microglia. Our study indicates that novel mechanisms are responsible for the immunomodulatory effect of MSCs on microglia and that MSCs, as well as TSG-6, might be promising therapeutic agents for the treatment of neurotraumatic injuries or neuroinflammatory diseases associated with microglial activation.

Dataset Information

MiR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis.

Publications

miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis.

Similar Datasets

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