Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells.
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.
Shouda
Takanori
T
Department of Orthopedic Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Hiraoka
Koji
K
Komiya
Setsuro
S
Hamada
Tetsuya
T
Zenmyo
Michihisa
M
Iwasaki
Hiroshi
H
Isayama
Teruto
T
Fukushima
Nobuhiro
N
Nagata
Kensei
K
Yoshimura
Akihiko
A
D000368:Aged; D019898:Autocrine Communication; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D005260:Female; D005799:Genes, Dominant; D051677:Histiocytoma, Malignant Fibrous / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D020032:Tyrphostins; D000093242:Interleukin-6 Inhibitors; C106644:SOCS3 protein, human; C494086:STAT3 protein, human; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide