Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells

Takanori Shouda, Koji Hiraoka, Setsuro Komiya, Tetsuya Hamada, Michihisa Zenmyo, Hiroshi Iwasaki, Teruto Isayama, Nobuhiro Fukushima, Kensei Nagata, Akihiko Yoshimura

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Abstract

There is no established optimum treatment for malignant fibrous histiocytoma (MFH) at present, and few MFH cell lines are established. In the present study, we established new MFH cell lines, KHZ-MFH and SFT85-03, and investigated the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway. We found that MFH cells secreted high levels of IL-6 and that STAT3 was constitutively activated in these cells. The JAK2 kinase inhibitor, tyrphostin AG490, suppressed the growth of MFH cells and inhibited the secretion of IL-6. Furthermore, blockade of activated STAT3 by forced expression of a cytokine signaling repressor, SOCS3 gene as well as a dominant-negative STAT3 in these cells significantly suppressed their growth. These results indicated that an autocrine mechanism of the JAK/STAT3 signaling pathway could promote the growth of MFH cells and that this pathway could be a therapeutic target of MFH.

Original languageEnglish
Pages (from-to)176-184
Number of pages9
JournalCancer Letters
Volume231
Issue number2
DOIs
Publication statusPublished - 2006 Jan 18

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Keywords

  • Malignant fibrous histiocytoma
  • RT-PCR
  • Tumor cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Shouda, T., Hiraoka, K., Komiya, S., Hamada, T., Zenmyo, M., Iwasaki, H., Isayama, T., Fukushima, N., Nagata, K., & Yoshimura, A. (2006). Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells. Cancer Letters, 231(2), 176-184. https://doi.org/10.1016/j.canlet.2005.01.042