IL-12 could induce monocytic tumor cells directional differentiation

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• 作者：Ting-ting Ma (1)
  Bi-Tao Wu (1)
  Yan Lin (1)
  Hai-Yu Xiong (1)
  Qin Wang (1)
  Zi-Wei Li (1)
  Feng Cheng (1)
  Zhi-Guang Tu (1)
  
  1. College of Laboratory Medicine ; Key Laboratory of Laboratory Medical Diagnostics of Education Ministry ; Chongqing Medical University ; Chongqing ; 400016 ; China
  
• 关键词：IL ; 12 ; Monocytic tumor cells ; Directional differentiation ; Macrophage ; like cells
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：402
• 期：1-2
• 页码：157-169
• 全文大小：1,920 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Medical Biochemistry
  Oncology
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4919

文摘

Interleukin-12 (IL-12), a member of interleukin family, plays a critical role in immune responses and anti-tumor activity. In this study, the effects of IL-12 on monocytic tumor cell lines differentiation to macrophagocyte and its likely mechanism was investigated. We examined the differentiation markers, morphological and functional changes, and possible mechanism in IL-12-treated THP-1 and U937 cells. It was found that IL-12 could up-regulated macrophage surface marker CD68 and CD11b expression in a time-dependent manner. Morphologically, after IL-12 treatment, THP-1 and U937 cells became round or irregular shape, even stretched many cell membrane protuberances; some cell nuclei became fuzzy or completely disappeared, and the chromatin appeared dense and cordlike. Furthermore, IL-12-induced monocytic tumor cell differentiation was accompanied by the growth arrest with G1-phase accumulation and S-phase reduction; apoptosis increased with anti-apoptosis protein Bcl-2 down-expression and pro-apoptosis protein Fas up-regulation, and enhanced phagocytosis function. The IL-12-induced macrophage differentiation of THP-1 and U937 cells was associated with the up-regulation of c-fms expression and the CSF-1R Tyr 809 site phosphorylation. These findings have revealed that IL-12 could induce monocytic tumor cells directional differentiation into macrophage-like cells, and its mechanism is possible connected with the up-regulation of c-fms expression and the phosphorylation of CSF-1R Tyr-809 site.