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.
authors.affiliation: Department of Orthopedic Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Shouda
authors.forename: Koji
authors.initials: K
authors.lastname: Hiraoka
authors.forename: Setsuro
authors.initials: S
authors.lastname: Komiya
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamada
authors.forename: Michihisa
authors.initials: M
authors.lastname: Zenmyo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Teruto
authors.initials: T
authors.lastname: Isayama
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fukushima
authors.forename: Kensei
authors.initials: K
authors.lastname: Nagata
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: 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
chemical_list: 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