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Article

Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1

  • Authors:
    • Jing Jia
    • Haibao Zhang
    • Lin He
    • Hongke Zhang
    • Maoguo Shu
  • View Affiliations / Copyright

    Affiliations: Department of Plastic, Cosmetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 1319-1330
    |
    Published online on: February 21, 2020
       https://doi.org/10.3892/or.2020.7513
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Abstract

Cutaneous neurofibromas (cNFs) are present in the majority of patients with neurofibromatosis type 1 (NF1), and results in disfigurements of the body, which is associated with psychological distress. A hallmark feature of cNF is the infiltration of inflammatory cells, among which macrophages are an important component of the microenvironment. Loss of neurofibromin (Nf1) expression results in activation of the PI3K and MAPK signaling pathways; however, the therapeutic effects of specific inhibitors targeting these pathways are not satisfactory. The present study showed increased macrophage infiltration accompanied by activation of effectors of the Hippo signaling pathway. Additionally, it was shown that XMU‑MP‑1 enhanced macrophage accumulation, in vivo and in vitro, by elevating the levels of C‑C motif chemokine ligand 5 (CCL5) and transforming growth factor (TGF)‑β1 expression. However, neither CCL5 nor TGF‑β1 ablation alone were able to effectively reverse the XMU‑MP‑1‑induced upregulation of macrophage accumulation, whereas concurrent ablation of these two genes significantly decreased macrophage accumulation. EdU staining and flow cytometry suggested that activated Yes‑associated protein 1 promoted proliferation rather than inhibiting apoptosis in macrophage cells, and this may underlie the increase in the accumulation of macrophages. Both CCL5/C‑C motif chemokine receptor 5 and TGF‑β1/TGFβ1 receptor served crucial roles in modulating macrophage proliferation, which ultimately contributed to macrophage accumulation. The function of the Hippo pathway in the development of cNF development and its potency as a therapeutic target merit further investigation.
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Copy and paste a formatted citation
Spandidos Publications style
Jia J, Zhang H, He L, Zhang H and Shu M: Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1. Oncol Rep 43: 1319-1330, 2020.
APA
Jia, J., Zhang, H., He, L., Zhang, H., & Shu, M. (2020). Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1. Oncology Reports, 43, 1319-1330. https://doi.org/10.3892/or.2020.7513
MLA
Jia, J., Zhang, H., He, L., Zhang, H., Shu, M."Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1". Oncology Reports 43.4 (2020): 1319-1330.
Chicago
Jia, J., Zhang, H., He, L., Zhang, H., Shu, M."Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1". Oncology Reports 43, no. 4 (2020): 1319-1330. https://doi.org/10.3892/or.2020.7513
Copy and paste a formatted citation
x
Spandidos Publications style
Jia J, Zhang H, He L, Zhang H and Shu M: Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1. Oncol Rep 43: 1319-1330, 2020.
APA
Jia, J., Zhang, H., He, L., Zhang, H., & Shu, M. (2020). Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1. Oncology Reports, 43, 1319-1330. https://doi.org/10.3892/or.2020.7513
MLA
Jia, J., Zhang, H., He, L., Zhang, H., Shu, M."Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1". Oncology Reports 43.4 (2020): 1319-1330.
Chicago
Jia, J., Zhang, H., He, L., Zhang, H., Shu, M."Cutaneous neurofibroma cells with active YAP promotes proliferation of macrophages resulting in increased accumulation of macrophages by modulating CCL5 and TGF‑β1". Oncology Reports 43, no. 4 (2020): 1319-1330. https://doi.org/10.3892/or.2020.7513
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