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.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Antibodies, Monoclonal / therapeutic use
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Apoptosis / genetics
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Bone Neoplasms / genetics
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Bone Neoplasms / metabolism
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Bone Neoplasms / pathology
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Bone Neoplasms / therapy*
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Cell Cycle Checkpoints / genetics
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Cell Growth Processes
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism
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Child
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Cytokines / antagonists & inhibitors*
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Cytokines / deficiency*
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Cytokines / genetics
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Cytokines / metabolism
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Female
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Gene Knockdown Techniques / methods
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Humans
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Lung Neoplasms / prevention & control*
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Lung Neoplasms / secondary*
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Male
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Middle Aged
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Midkine
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Molecular Targeted Therapy
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Osteosarcoma / genetics
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Osteosarcoma / metabolism
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Osteosarcoma / secondary
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Osteosarcoma / therapy*
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RNA, Small Interfering / administration & dosage
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RNA, Small Interfering / genetics
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Sarcoma / genetics
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Sarcoma / metabolism
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Sarcoma / pathology
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Sarcoma / therapy*
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Tumor Cells, Cultured
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Young Adult
Substances
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Antibodies, Monoclonal
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Cytokines
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RNA, Small Interfering
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Midkine