Therapeutic approaches targeting midkine suppress tumor growth and lung metastasis in osteosarcoma

Abstract Midkine (MK) plays important roles in tumorigenesis, however, the biological function of MK and whether MK can be a therapeutic target in osteosarcoma are unclear. Here, we found that osteosarcoma tissues showed high MK expression. MK knockdown by small interfering RNA significantly induced...

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Veröffentlicht in:Cancer letters 2012-03, Vol.316 (1), p.23-30
Hauptverfasser: Sueyoshi, Takanao, Jono, Hirofumi, Shinriki, Satoru, Ota, Kazutoshi, Ota, Tomoko, Tasaki, Masayoshi, Atsuyama, Eri, Yakushiji, Toshitake, Ueda, Mitsuharu, Obayashi, Konen, Mizuta, Hiroshi, Ando, Yukio
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Sprache:eng
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Zusammenfassung:Abstract Midkine (MK) plays important roles in tumorigenesis, however, the biological function of MK and whether MK can be a therapeutic target in osteosarcoma are unclear. Here, we found that osteosarcoma tissues showed high MK expression. MK knockdown by small interfering RNA significantly induced apoptosis in osteosarcoma cells, whereas recombinant MK increased cell proliferation. Inhibition of MK signaling by anti-MK monoclonal antibody (anti-MK mAb) suppressed growth of osteosarcoma cells both in vitro and in vivo . Moreover, inhibition of MK function significantly suppressed lung metastasis in xenograft transplantation model. Targeting MK by anti-MK mAb may have value in the treatment of osteosarcoma.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2011.10.013