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Expression of Macrophage Migration Inhibitory Factor Relates to Survival in High-grade Osteosarcoma

  • Symposium: Molecular Genetics in Sarcoma
  • Published:
Clinical Orthopaedics and Related Research

Abstract

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is implicated in many aspects of tumor progression, including cell proliferation, invasion, and angiogenesis. We asked if MIF expression predicts survival and if it is associated with angiogenesis and cell invasion in osteosarcoma. We performed immunohistochemistry for MIF expression in prechemotherapy biopsy specimens of 58 patients with osteosarcoma. To investigate the role of MIF in angiogenesis, microvessel density was measured and compared with MIF expression. We also treated osteosarcoma cell lines (U2-OS and MG63) with MIF and measured vascular endothelial growth factor, a potent proangiogenic factor, by enzyme-linked immunosorbent assay. To study the role of MIF in cell invasion, Boyden chamber assay was performed after knockdown of MIF by short interfering RNA. MIF independently predicted overall survival and metastasis-free survival. MIF expression correlated with microvessel density and induced a dose-dependent increase in vascular endothelial growth factor. Knockdown of MIF by short interfering RNA resulted in decreased cell invasion. These results suggest MIF could serve as a prognostic marker and a potential therapeutic target for osteosarcoma.

Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, 110-744, Seoul, Korea

    Ilkyu Han MD, PhD, Mi Ra Lee BS, Joo Han Oh MD, PhD & Han-Soo Kim MD, PhD

  2. Clinical Research Institute of Seoul National University Hospital, Seoul, Korea

    Mi Ra Lee BS

  3. Department of Orthopedic Surgery, Cheju National University, Jeju-si, Jeju-do, Korea

    Kwang Woo Nam MD

  4. Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea

    Joo Han Oh MD, PhD

  5. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

    Kyung Chul Moon MD, PhD

Authors
  1. Ilkyu Han MD, PhD
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  2. Mi Ra Lee BS
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  3. Kwang Woo Nam MD
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  4. Joo Han Oh MD, PhD
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  5. Kyung Chul Moon MD, PhD
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  6. Han-Soo Kim MD, PhD
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Corresponding author

Correspondence to Han-Soo Kim MD, PhD.

Additional information

One or more of the authors (JHO, HSK) have received funding from a grant (No 02-2006-020) from the Seoul National University Hospital Research Fund, Korea.

Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

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Han, I., Lee, M.R., Nam, K.W. et al. Expression of Macrophage Migration Inhibitory Factor Relates to Survival in High-grade Osteosarcoma. Clin Orthop Relat Res 466, 2107–2113 (2008). https://doi.org/10.1007/s11999-008-0333-1

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  • DOI: https://doi.org/10.1007/s11999-008-0333-1

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