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

doi:10.1016/j.canlet.2005.01.042

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

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

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 language	English
Pages (from-to)	176-184
Number of pages	9
Journal	Cancer Letters
Volume	231
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2005.01.042
Publication status	Published - 2006 Jan 18
Externally published	Yes

Keywords

Malignant fibrous histiocytoma
RT-PCR
Tumor cells

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.canlet.2005.01.042

Cite this

@article{2edd9183b8104ca1a595fc69b520ed55,

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

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.",

keywords = "Malignant fibrous histiocytoma, RT-PCR, Tumor cells",

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

note = "Funding Information: We thank Ms Y. Kawabata for technical assistance and Ms Y. Nishi for manuscript preparation. This work was supported by special grants-in-aid from the Ministry of Education, Science, Technology, Sports, and Culture of Japan, the Haraguchi Memorial Foundation, the Yamanouchi Foundation for Research on Metabolic Disorders, the Takeda Science Foundation, the Mochida Memorial Foundation, the Kato Memorial Foundation, Haraguchi Memorial Foundation and the Uehara Memorial Foundation.",

year = "2006",

month = jan,

day = "18",

doi = "10.1016/j.canlet.2005.01.042",

language = "English",

volume = "231",

pages = "176--184",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

TY - JOUR

T1 - Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells

AU - Shouda, Takanori

AU - Hiraoka, Koji

AU - Komiya, Setsuro

AU - Hamada, Tetsuya

AU - Zenmyo, Michihisa

AU - Iwasaki, Hiroshi

AU - Isayama, Teruto

AU - Fukushima, Nobuhiro

AU - Nagata, Kensei

AU - Yoshimura, Akihiko

N1 - Funding Information: We thank Ms Y. Kawabata for technical assistance and Ms Y. Nishi for manuscript preparation. This work was supported by special grants-in-aid from the Ministry of Education, Science, Technology, Sports, and Culture of Japan, the Haraguchi Memorial Foundation, the Yamanouchi Foundation for Research on Metabolic Disorders, the Takeda Science Foundation, the Mochida Memorial Foundation, the Kato Memorial Foundation, Haraguchi Memorial Foundation and the Uehara Memorial Foundation.

PY - 2006/1/18

Y1 - 2006/1/18

N2 - 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.

AB - 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.

KW - Malignant fibrous histiocytoma

KW - RT-PCR

KW - Tumor cells

UR - http://www.scopus.com/inward/record.url?scp=29844433086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29844433086&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2005.01.042

DO - 10.1016/j.canlet.2005.01.042

M3 - Article

C2 - 16399222

AN - SCOPUS:29844433086

SN - 0304-3835

VL - 231

SP - 176

EP - 184

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this