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首页> 外文期刊>Cell cycle >Kaposi's sarcoma-associated herpesvirus infection promotes differentiation and polarization of monocytes into tumor-associated macrophages
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Kaposi's sarcoma-associated herpesvirus infection promotes differentiation and polarization of monocytes into tumor-associated macrophages

机译：Kaposi的肉瘤相关的Herpesvirus感染促进单核细胞的分化和极化进入肿瘤相关的巨噬细胞

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摘要

Tumor associated macrophages (TAMs) promote angiogenesis, tumor invasion and metastasis, and suppression of anti-tumor immunity. These myeloid cells originate from monocytes, which differentiate into TAMs upon exposure to the local tumor microenvironment. We previously reported that Kaposi's sarcoma-associated herpes virus (KSHV) infection of endothelial cells induces the cytokine angiopoietin-2 (Ang-2) to promote migration of monocytes into tumors. Here we report that KSHV infection of endothelial cells induces additional cytokines including interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) that drive monocytes to differentiate and polarize into TAMs. The KSHV-induced TAMs not only express TAM-specific markers such as CD-163 and legumain (LGMN) but also display a gene expression profile with characteristic features of viral infection. More importantly, KSHV-induced TAMs enhance tumor growth in nude mice. These results are consistent with the strong presence of TAMs in Kaposi's sarcoma (KS) tumors. Therefore, KSHV infection of endothelial cells generates a local microenvironment that not only promotes the recruitment of monocytes but also induces their differentiation and polarization into TAMs. These findings reveal a new mechanism of KSHV contribution to KS tumor development.
机译：肿瘤相关的巨噬细胞（TAMS）促进血管生成，肿瘤侵袭和转移，抑制抗肿瘤免疫力。这些骨髓细胞源自单核细胞，在暴露于局部肿瘤微环境时分化为TAMS。我们之前报道，Kaposi的肉瘤相关疱疹病毒（KSHV）内皮细胞感染诱导细胞因子血管发球率素-2（Ang-2）促进单核细胞的迁移到肿瘤中。在这里，我们报告的内皮细胞Kshv感染诱导包括白细胞介素-6（IL-6），白细胞介素-10（IL-10）和白细胞介素-13（IL-13）的额外细胞因子，其驱动单核细胞以区分和偏振成Tams。 KSHV诱导的TAM不仅表达了特异性标记，例如CD-163和肉豆蔻（LGMN），而且还显示了具有病毒感染的特征特征的基因表达谱。更重要的是，KSHV诱导的TAMS增强裸鼠肿瘤生长。这些结果与Kaposi的肉瘤（KS）肿瘤中的TAMS的强烈存在一致。因此，内皮细胞的KSHV感染产生局部微环境，不仅促进单核细胞的募集，而且还诱导其分化和极化进入TAMS。这些发现揭示了KSHV对KS肿瘤发育的新机制。

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  • 来源
    《Cell cycle》 |2017年第17期|共11页
  • 作者

    Bhaskaran Natarajan; Ghosh Santosh K.; Yu Xiaolan; Qin Sanhai; Weinberg Aaron; Pandiyan Pushpa; Ye Fengchun;

  • 作者单位

    Case Western Reserve Univ Sch Dent Med Dept Biol Sci 10900 Euclid Ave Cleveland OH 44106 USA;

    Case Western Reserve Univ Sch Dent Med Dept Biol Sci 10900 Euclid Ave Cleveland OH 44106 USA;

    Case Western Reserve Univ Sch Dent Med Dept Biol Sci 10900 Euclid Ave Cleveland OH 44106 USA;

    Case Western Reserve Univ Sch Dent Med Dept Biol Sci 10900 Euclid Ave Cleveland OH 44106 USA;

    Case Western Reserve Univ Sch Dent Med Dept Biol Sci 10900 Euclid Ave Cleveland OH 44106 USA;

    Case Western Reserve Univ Sch Dent Med Dept Biol Sci 10900 Euclid Ave Cleveland OH 44106 USA;

    Case Western Reserve Univ Sch Dent Med Dept Biol Sci 10900 Euclid Ave Cleveland OH 44106 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Kaposi's sarcoma; KSHV; monocytes; tumor-associated macrophages;

    机译：Kaposi的肉瘤;KSHV;单核细胞;肿瘤相关的巨噬细胞;

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