title: 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 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.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takanao
authors.initials: T
authors.lastname: Sueyoshi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinriki
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Ota
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ota
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.forename: Eri
authors.initials: E
authors.lastname: Atsuyama
authors.forename: Toshitake
authors.initials: T
authors.lastname: Yakushiji
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuta
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D048708:Cell Growth Processes; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D058990:Molecular Targeted Therapy; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D034741:RNA, Small Interfering; D000078792:Midkine