THE ANALYSIS OF TOLL-LIKE RECEPTOR SIGNAL PATHWAY IN HUMAN OVARIAN CANCER CELLS

  • HAYASHI Masaki
    Department of Obstetrics and Gynecology, Showa University School of Medicine
  • OKUDA Tsuyoshi
    Department of Obstetrics and Gynecology, Showa University School of Medicine
  • CHIBA Hiroshi
    Department of Obstetrics and Gynecology, Showa University School of Medicine
  • NAGATSUKA Masaaki
    Department of Obstetrics and Gynecology, Showa University School of Medicine
  • OKAI Takashi
    Department of Obstetrics and Gynecology, Showa University School of Medicine

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  • ヒト卵巣癌細胞株におけるToll-like receptorシグナルパスウェイの解析
  • ヒト ランソウガン サイボウカブ ニ オケル Toll like receptor シグナルパスウェイ ノ カイセキ

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Inflammation has been implicated in the initiation and progression of ovarian cancer, although the mechanisms underlying this effect are still unclear. Toll-like receptors (TLRs) allow immune cells to recognize pathogens and to trigger inflammatory responses. The tumor cell expression of TLRs can promote inflammation and cell survival in the tumor microenvironment. The present study evaluated the changes in 84 genes involved in the TLR pathway using a real time PCR array in 4 different histological types of ovarian cancer cells. The functional activity for TLRs was also demonstrated by the stimulation of cell lines with specific agonists and release of the proinflammatory cytokines interleukin-6 and CCL-2. The results are as follows: TLR6, 7, 8, 10 were upregulated in serous carcinoma cells; in particular, there was 15.9-fold over-expression of TLR7. TLR4 was upregulated in mucinous carcinoma cells. In contrast, there was no upregulation of TLRs nor down regulation of TLRs while a downregulation of MyD88 TLR adaptor genes was observed in clear cell carcinoma cells. The TLRs that were upregulated in these cells were functional, except for TLR7 in serous adenocarcinoma. In endometrioid carcinoma cells in which no TLRs were upregulated without stimulation, IL-6 and CCL-2 were induced by TLR5. On the other hand, no induction of proinflammatory cytokines was observed in clear cell carcinoma cells.These results suggest that TLRs appear to play a role in the development and proliferation of ovarian cancer cells, and each histological type of TLR may differently manipulate the inflammatory pathway through TLRs to thereby characterize their biological properties.

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