Cancer cell-derived IL-8 induces monocytic THP1 cells to secrete IL-8 via the mitogen-activated protein kinase pathway

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• 作者：Yukina Nishio ; Takahiro Gojoubori ; Yasuhide Kaneko ; Noriyoshi Shimizu…
• 关键词：Oral squamous cell carcinoma ; Interleukin ; 8 ; Macrophage ; Mitogen ; activated protein kinase
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：36
• 期：12
• 页码：9171-9177
• 全文大小：617 KB
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• 作者单位：Yukina Nishio (1)
  Takahiro Gojoubori (2)
  Yasuhide Kaneko (2)
  Noriyoshi Shimizu (3)
  Masatake Asano (2)
  
  1. Division of Oral Structural and Functional Biology, Nihon University Graduate School of Dentistry, Tokyo, Japan
  2. Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan
  3. Department of Orthodontics, Nihon University School of Dentistry, Tokyo, Japan
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

Aberrant activity of transcription factors in oral squamous cell carcinoma (OSCC) results in the spontaneous secretion of various cytokines and chemokines. Among them, IL-8, owing to its angiogenic activity, promotes the growth of OSCCs. In the present study, we examined the role of IL-8 secreted by OSCCs, on the angiogenic activity of monocytic THP1 cells. Culture supernatant (Ca-sup) augmented IL-8 secretion by THP1 cells, which was found to be significantly reduced following the removal Ca9-22-derived IL-8 from the Ca-sup. IL-8 induction was regulated at the transcriptional level, because real-time PCR demonstrated the augmented IL-8 messenger RNA (mRNA) expression. We further performed the luciferase assay using the 5′-untranslated region of IL-8 gene. Contradictory to our speculations, luciferase activity was not augmented by Ca-sup stimulation. NF-κB-independent IL-8 induction was further confirmed by pre-treating THP1 cells with NF-κB-specific inhibitors. To elucidate the signaling pathway, THP1 was pre-treated with MEK inhibitors. The results demonstrated that pre-treatment of cells with MEK inhibitor drastically reduced IL-8 levels, suggesting the role of MEK. Moreover, Ca-sup was found to increase ERK1/2 phosphorylation in a time-dependent manner. These results indicated that OSCC-derived IL-8 appears to activate angiogenic activity in monocytes within the tumor microenvironment via the mitogen-activated protein kinase (MAPK) pathway. Keywords Oral squamous cell carcinoma Interleukin-8 Macrophage Mitogen-activated protein kinase