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

Cancer Lett. 2012 Mar;316(1):23-30. doi: 10.1016/j.canlet.2011.10.013. Epub 2011 Oct 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Apoptosis / genetics
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Bone Neoplasms / therapy*
  • Cell Cycle Checkpoints / genetics
  • Cell Growth Processes
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Child
  • Cytokines / antagonists & inhibitors*
  • Cytokines / deficiency*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Knockdown Techniques / methods
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary*
  • Male
  • Middle Aged
  • Midkine
  • Molecular Targeted Therapy
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / secondary
  • Osteosarcoma / therapy*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Sarcoma / genetics
  • Sarcoma / metabolism
  • Sarcoma / pathology
  • Sarcoma / therapy*
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • RNA, Small Interfering
  • Midkine