GLI2 is a novel therapeutic target for metastasis of osteosarcoma. Issue 6 (8th August 2014)

• Record Type: Journal Article
• Authors: Nagao‐Kitamoto, Hiroko; Nagata, Masahito; Nagano, Satoshi; Kitamoto, Sho; Ishidou, Yasuhiro; Yamamoto, Takuya; Nakamura, Shunsuke; Tsuru, Arisa; Abematsu, Masahiko; Fujimoto, Yusuke; Yokouchi, Masahiro; Kitajima, Shinichi; Yoshioka, Takako; Maeda, Shingo; Yonezawa, Suguru; Komiya, Setsuro; Setoguchi, Takao
• Is Part Of: International journal of cancer. Volume 136:Issue 6(2015:Mar. 15)
• Page Start: 1276
• Page End: 1284
• Publication Date: 2014-08-08
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29107
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Aberrant activation of the Hedgehog (Hh) pathway has been reported in several malignancies. We previously demonstrated that knockdown of <italic>GLI2</italic> inhibited proliferation of osteosarcoma cells through regulation of the cell cycle. In this study, we analyzed the function of <italic>GLI2</italic> in the pathogenesis of osteosarcoma metastasis. Immunohistochemical studies showed that GLI2 was overexpressed in patient osteosarcoma specimens. Knockdown of <italic>GLI2</italic> inhibited migration and invasion of osteosarcoma cells. In contrast, the forced expression of constitutively active <italic>GLI2</italic> in mesenchymal stem cells promoted invasion. In addition, xenograft models showed that knockdown of <italic>GLI2</italic> decreased lung metastasis of osteosarcomas. To examine clinical applications, we evaluated the efficacy of arsenic trioxide (ATO), which is a Food and Drug Administration‐approved antitumor drug, on osteosarcoma cells. ATO treatment suppressed the invasiveness of osteosarcoma cells by inhibiting the transcriptional activity of <italic>GLI2</italic>. In addition, the combination of Hh inhibitors including ATO, vismodegib and GANT61 prevented migration and metastasis of osteosarcoma cells. Consequently, our findings suggested that <italic>GLI2</italic> regulated metastasis as well as the progression of osteosarcomas. Inhibition of the GLI2 transcription may be an effective therapeutic method for preventing osteosarcoma metastasis.</p> </abstract>